Pregnenolone sulphate improves memory processing in early-handled female rats

Early life experiences lead to sex-specific behavioural and neurochemical changes in adulthood. Indeed, early handling enhances learning and memory in male rats (Cannizzaro et al., 2005), whereas it impairs learning performance in female adult rats, a finding that has been correlated to decreased nitric oxide (NO) production in the hippocampus (Noschang et al., 2010). Pregnenolone sulfate (PREGS) is considered as one of the most potent memory-enhancing neurosteroids, since its activity as a potent positive modulator of N-methyl-d-aspartate receptors (NMDARs) and a negative modulator of gamma-aminobutyric acid(A) receptors (GABA(A)Rs) (Vallée et al., 2001). Given these premises, this study a…

Behavioural and pharmacological characterization of a novel cannabimimetic adamantane-derived indole, APICA, in C57BL/6J mice

The novel adamantane derivative APICA (N-(adamtan-1-yl)-1-pentyl-1H-indole-3-carboxamide) was recently identified as a cannabimimetic indole of abuse (1, 2). Despite its novel structure, APICA recalls cannabimimetic indoles, such as representative member JWH-018. The emerging abuse problem, together with the paucity of information about the bioactivity of APICA (3) emphasize the need for further evaluation of the in vivo pharmacology of this novel indole-derived compound. In the present study, the effects of APICA (0 - 1 - 3 mg/Kg, i.p.) were tested in C57BL/6J mice, in a battery of tests that are sensitive to the effects of psychoactive cannabinoids, including body temperature; locomotor a…

PATHOLOGICAL GAMBLING: AN ASSOCIATION WITH ALEXITHYMIA, PERSONALITY DISORDERS AND CLINICAL SYNDROMES

Pathological gambling (PG) is a disorder recently conceptualized as a behavioural addiction, because of its neurobiological, neurophysiological and psychological features (American Psychiatric Association. Diagnostic and statistical manual of mental disorders - 5th ed., 2013; Potenza et al., 2012). PG represents both a social and a sanitary cost, in terms of pharmacological and psychological therapies. The aim of this study was to examine the correlation between personality disorders, clinical syndromes and alexithymia levels in a group of pathological gamblers. Furthermore this study aimed at highlighting a relationship between PG and alexithymia, over and above the relationship between pe…

A new “sudden fright paradigm” to explore the role of (epi)genetic modulations of the DAT gene in fear-induced avoidance behavior

Alterations in dopamine (DA) reuptake are involved in several psychiatric disorders whose symptoms can be investigated in knock out rats for the DA transporter (DAT-KO). Recent studies evidenced the role of epigenetic DAT modulation in depressive-like behavior. Accordingly, we used heterozygous (HET) rats born from both HET parents (termed MIX-HET), compared to HET rats born from WT-mother and KO-father (MAT-HET), implementing the role of maternal care on DAT modulation. We developed a "sudden fright" paradigm (based on dark-light test) to study reaction to fearful inputs in the DAT-KO, MAT-HET, MIX-HET, and WT groups. Rats could freely explore the whole 3-chambers apparatus; then, they wer…

Acetaldehyde as a drug of abuse: insight into AM281 administration on operant-conflict paradigm in rats

Increasing evidence focuses on acetaldehyde (ACD) as the mediator of the rewarding and motivational properties of ethanol. Indeed, ACD stimulates dopamine release in the nucleus accumbens and it is self-administered under different conditions. Besides the dopaminergic transmission, the endocannabinoid system has been reported to play an important role in ethanol central effects, modulating primary alcohol rewarding effect, drug-seeking and relapse behaviour. Drug motivational properties are highlighted in operant paradigms which include response-contingent punishment, a behavioural equivalent of compulsive drug use despite adverse consequences. The aim of this study was thus to characterize…

Epigenetic regulation of sex differences in susceptibility to stress

Under current diagnostics depression and stress related mood disorders have a higher occurrence in women than men. Little is known of the biological mechanisms contributing to these sex differences and how they may impact potential new therapeutics. Here we examine how DNA methylation contributes to sex specific stress vulnerability in adult animals. Mice of both sexes were exposed to variable stress and given a behavioral test battery to examine stress sensitivity. Female mice expressed depressionassociated behavior across all tests stress exposure whereas males were behaviorally resilient. Markers of pre and post-synaptic plasticity and spine morphology were examined using a combination o…

Manipulation of the DA signal on the onset of relapse of ACD

It's widely known that all addictive drugs show analogous pathological behaviours consisting in compulsive drug seeking,loss of self –control and propensity to relapse. This evidence is suggestive of a common brain mechanism involving the Ventral Tegmental Area and Nucleus Accumbens whereby mesocorticolimbimc dopamine pathway. Dfferent and apparently anthitetic classes of drugs of abuse manage to increase DA release, in the aforementioned areas (Di Chiara, 1988; 1995). Reductions in activity of the mesolimbic dopamine system in the nucleus accumbes occur during drug withdrawal in animal studies (Weiss F et al. 1992; 1996). Experimental evidences have proven D2 receptor involvement in drug s…

Reward-related limbic memory and stimulation of the cannabinoid system: An upgrade in value attribution?

While a lot is known about the mechanisms promoting aversive learning, the impact of rewarding factors on memory has received comparatively less attention. This research investigates reward-related explicit memory in male rats, by taking advantage of the emotional-object recognition test. This is based on the prior association, during conditioned learning, between a rewarding experience (the encounter with a receptive female rat) and an object; afterwards rat discrimination and recognition of the â emotional objectâ is recorded in the presence of a novel object, as a measure of positive limbic memory formation. Since endocannabinoids are critical for processing reward and motivation, the co…

Mothering under the influence: How perinatal drugs of abuse alter the mother-infant interaction

AbstractAlthough drug-abusing women try to moderate their drug and alcohol use during pregnancy, they often relapse at a time when childcare needs are high and maternal bonding is critical to an infant’s development. In the clinical setting, the search for the neural basis of drug-induced caregiving deficits is complex due to several intervening variables. Rather, the preclinical studies that control for drug dose and regimen, as well as for gestational and postpartum environment, allow a precise determination of the effects of drugs on maternal behaviour. Given the relevance of the issue, this review will gather reports on the phenotypic correlates of maternal behaviour in preclinical stud…

The role of pregnenolone sulphate in spatial orientation-acquisition and retention: An interplay between cognitive potentiation and mood regulation

Abstract Neurosteroids can alter neuronal excitability interacting with specific neurotransmitter receptors, thus affecting several functions such as cognition and emotionality. In this study, we investigated, in adult male rats, the effects of the acute administration of pregnenolone-sulfate (PREGS) (10 mg/Kg, s. c.) on cognitive processes using the Can test, a non aversive spatial/visual task which allows the assessment of spatial information-acquisition during the baseline training, and of memory retention in the longitudinal study. Furthermore, on the basis of PREGS pharmacological profile, the modulation of depressive-like behaviour was also evaluated in the forced swim test (FST). Our…

DHA protects PC12 cells against oxidative stress and apoptotic signals through the activation of the NFE2L2/HO-1 axis

Docosahexaenoic acid (DHA) is an omega‑3 polyunsaturated fatty acid, derived mainly from fish oil. It is well known that DHA is present in high concentrations in nervous tissue and plays an important role in brain development and neuroprotection. However, the molecular mechanisms underlying its role remain to be fully elucidated. In this study, to enhance our understanding of the pathophysiological role of DHA, we investigated the possible neuroprotective mechanisms of action of DHA against hydrogen peroxide (H2O2)‑induced oxidative damage in a rat pheochromocytoma cell line (PC12). Specifically, we evaluated the viability, oxidation potential, and the expression and production of antioxida…

Prenatal Exposure to Δ9-Tetrahydrocannabinol Affects Hippocampus-Related Cognitive Functions in the Adolescent Rat Offspring: Focus on Specific Markers of Neuroplasticity

Previous evidence suggests that prenatal exposure to THC (pTHC) derails the neurodevelopmental trajectories towards a vulnerable phenotype for impaired emotional regulation and limbic memory. Here we aimed to investigate pTHC effect on hippocampus-related cognitive functions and markers of neuroplasticity in adolescent male offspring. Wistar rats were exposed to THC (2 mg/kg) from gestational day 5 to 20 and tested for spatial memory, object recognition memory and reversal learning in the reinforce-motivated Can test and in the aversion-driven Barnes maze test; locomotor activity and exploration, anxiety-like behaviour, and response to natural reward were assessed in the open field, elevate…

Bilateral Transcranial Magnetic Stimulation of the Prefrontal Cortex Reduces Cocaine Intake: A Pilot Study

Background Chronic cocaine consumption is associated with a decrease in mesolimbic dopamine transmission that maintains drug intake. transcranial magnetic stimulation (TMS) is gaining reliability, a useful therapeutic tool in drug addiction, since it can modulate cortico-limbic activity resulting in reduction of drug craving. Aims In the present study, we investigated the therapeutic effect of bilateral TMS of prefrontal cortex (PFC) in reducing cocaine intake, in a sample of treatment-seeking patients with current cocaine use disorder (DSM-V). Methods Ten cocaine addicts (DSM-V) were randomly assigned to the active or sham stimulation protocol in a double-blind experimental design. Twelve …

DA-Phen as a new potential DA-mimetic agent for treatment of alcohol addiction: preclinical in vivo studies

Rewarding and reinforcing properties of alcohol are mediated by activation of the mesolimbic dopaminergic system1. This neurosystem is hypofunctional in the addicted brain, even beyond somatic and psychological signs of withdrawal. Boosting strategy on the dopaminergic tone could represent a valid approach to alcohol addiction treatment2. The effects of a new dopamine conjugate3 (2-amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide, DA-Phen) on operant behaviour and on withdrawal behaviour, following alcohol deprivation, were evaluated. The concentration of acetaldehyde (ACD), ethanol's first metabolite, as an indirect measure of the possible DA-Phen modulation in alcohol consum…

Binge-like alcohol exposure in adolescence: behavioural, neuroendocrine and molecular evidence of abnormal neuroplasticity … and return

Binge alcohol consumption among adolescents affects the developing neural networks underpinning reward and stress processing in the nucleus accumbens (NAc). This study explores in rats the long-lasting effects of early intermittent exposure to intoxicating alcohol levels at adolescence, on: (1) the response to natural positive stimuli and inescapable stress

Evaluation of neuropeptide Y expression during acetaldehyde withdrawal in rats. Focus on hippocampus and nucleus accumbens

Stress-related neuropeptides are involved in setting up alcohol addiction. Ethanol is able to acutely induce CRH and ACTH release, while cronically a dampered response of the hypothalamus -pituitary- adrenal (HPA) axis has been observed. Also neuropeptide Y (NPY) has been shown to modulate ethanol consumption, and its central expression seems inversely correlated to ethanol intake. Recent in vivo and in vitro evidence have highlighted the key role of acetaldehyde (ACD), ethanol first metabolite, as a mediator of the central effects of ethanol, even as modulator of the neuropeptidergic transmission in the rat brain. The aim of this study was to investigate NPY immunoreactivity following a 4-…

Addictive-like behaviour for Acetaldehyde: involvement of D2 receptors

Acetaldehyde (ACD), ethanol's first metabolite, is centrally active and shows rewarding and motivational properties. It is able to activate mesolimbic dopamine system, since it enhances neuronal firing of dopamine cells in ventral tegmental area and exerts dopamine release in the nucleus accumbens (Foddai et al., 2004; Melis et al., 2007; Deehan et al., 2013). ACD motivational properties are demonstrated by self-administration studies in rodents (Rodd et al., 2005), particularly behavioural evidence suggests that ACD could produce positive reinforcing effects in operant-conflict paradigms (Cacace et al., 2012). In order to shed light on neurobiological substrate underpinning ACD-related beh…

Acetaldehyde and Motivation

Abstract Acetaldehyde contributes to alcohol’s neuroactive effects through its own motivational properties. This chapter gathers current evidence on acetaldehyde psychoactive action, focusing on behavioral investigations able to unveil acetaldehyde rewarding effects and their pharmacological modulation in vivo. Acetaldehyde induces conditioned place preference for paired environment and cues and is dose-dependently self-administered in a two-bottle choice drinking paradigm. Acetaldehyde’s motivational properties are further highlighted by operant paradigms tailored to model several addiction-like behaviors, such as induction and maintenance of operant responding, drug-seeking in extinction,…

Drinking pattern matters: effects on maternal care and offspring vulnerability to alcohol in rats

Alcohol drinking during pregnancy and post-partum period is a major concern because of the persistent neurobehavioral deficits in the offspring, which include increased vulnerability to substance abuse (1). The intermittent pattern of alcohol consumption induces higher drinking levels and deeper neurobiological changes in addiction-related brain regions, with respect to traditional free-access paradigms in male rats (2, 3). Nevertheless, no studies investigated on the effects of the drinking pattern on female subjects during pregnancy and perinatal time. To this aim, this study explored the consequences of continuous vs. intermittent drinking pattern on maternal behaviour and on offspring v…

FUNCTIONAL CONNECTIVITY OF THE CEREBELLUM INPATHOLOGICAL GAMBLER

Motor Transitions' Peculiarity of Heterozygous DAT Rats When Offspring of an Unconventional KOxWT Mating.

Abstract Causal factors of psychiatric diseases are unclear, due to gene × environment interactions. Evaluation of consequences, after a dopamine-transporter (DAT) gene knock-out (DAT-KO), has enhanced our understanding into the pathological dynamics of several brain disorders, such as Attention-Deficit/Hyperactivity and Bipolar-Affective disorders. Recently, our attention has shifted to DAT hypo-functional (heterozygous, HET) rodents: HET dams display less maternal care and HET females display marked hypo-locomotion if cared by HET dams (Mariano et al., 2019). We assessed phenotypes of male DAT-heterozygous rats as a function of their parents: we compared “maternal” origin (MAT-HET, obtain…

Erratum to “Motor Transitions' Peculiarity of Heterozygous DAT Rats When Offspring of An Unconventional KOxWT Mating” [Neuroscience 433C (2020) 108–120]

ETHANOL DRINKING PATTERN DIFFERENTLY AFFECTS NOVELTY-RELATED BEHAVIOUR DURING ABSTINENCE IN FEMALE RATS

Withdrawal from chronic ethanol leads to a multifaceted syndrome, characterized by negative affective state. Novelty seeking and motivation, closely related to affective state, can be assessed in rodents exploring behavioural response to novelty. This study aims at assessing novelty-related behaviour in female rats during ethanol withdrawal following different self-administration patterns. Female rats underwent 9-week-, 2-bottle choice-, continuous or intermittent (3 days/week) access to 20% ethanol; they were named CARs and IARs respectively. After 12h from last ethanol access, they were tested for locomotor activity induced by a novel environment; time spent in the central area of an open…

Intermittent- vs continuous alcohol access in female rats: Effects on deprivation phenotype and maternal behavior as a consequence of the drinking pattern

In male rats, the intermittent alcohol access paradigm produces relevant and specific consequences on neuronal activity and behavior, with respect to traditional free-access paradigms (Carnicella et al., 2014). In order to explore gender-related effects, this study aimed at assessing the consequences of two different patterns of alcohol self-administration on peculiar feminine behavioral repertoire, such as deprivation phenotype and maternal care. Animals underwent long-term, home cage, two-bottle “alcohol (20% v/v) or water” choice regimen, with continuous (7 days a week) or intermittent (3 days a week) access, and were tested for alcohol intake and preference. During acute deprivation, th…

DYSPHORIC-LIKE BEHAVIOUR DURING ETHANOL WITHDRAWAL IN FEMALE RATS. EFFECT OF CONTINUOUS VS INTERMITTENT ACCESS PARADIGM.

Women show higher vulnerability for neuroadaptation to alcohol, which may contribute to negative emotional state during withdrawal (Sharrett-Field et al., 2013; Koob and Le Moal, 1997). This study aimed at exploring the effects of different patterns of voluntary ethanol consumption on female rat"s affective behaviour during withdrawal. Female rats underwent 12-week-, 2-bottle choice- continuous or intermittent (3 days/week ) access to 20% ethanol and were respectively named CARs and IARs. They were tested for alcohol preference; dysphoric-like state during withdrawal (24-48h); depressive- and anhedonic-like behaviours explored by forced swim- and saccharin preference tests; anxiety-like beh…

Acetaldehyde as a drug of abuse: Involvement of endocannabinoid- and dopamine neurotransmission

Acetaldehyde (ACD), the first metabolite of ethanol, directly enhances dopamine neurotransmission (1) and has rewarding and motivational properties in paradigms tailored for studying addictive-like behaviours (2, 3). The endocannabinoid system affects distinct drug-related behaviours, since it may in turn fine-tune dopamine cell activity (4, 5). In light of this, the present study aimed at investigating the effects of a direct manipulation of the DAergic synapse, and the contribution of the endocannabinoid system on oral ACD self-administration in rats. ACD drinking-behaviour was evaluated in an operant paradigm consisting of acquisition and maintenance; extinction; deprivation and relapse;…

Perinatal alcohol intake, maternal behaviour and transgenerational inheritance of drug abuse; effects of drinking pattern and environmental enrichment

Alcohol drinking during pregnancy and post-partum is a major concern because of the persistent neurobehavioral deficits in the offspring that include increased vulnerability to substance abuse (McMurray et al., 2008). Moreover, the pattern of alcohol consumption accounts for specific neurobiological alterations that involve brain regions, that significantly overlap with those involved in maternal care behaviour (Stuber et al., 2008; George et al. 2012). Rodent studies on environmental enrichment have clearly demonstrated the capacity for non-drug modification of addiction-related behaviours (Nader et al., 2012). Thus, this study aimed at: (I) exploring the consequences of continuous vs. int…

Activity of orally self-administered acetaldehyde in an operant/conflict paradigm in rats; involvement of cannabinoid cb1 receptors

Acetaldehyde (ACD), ethanol first metabolite, interacts with the dopaminergic reward system, and with the neuropeptidergic transmission in the hypothalamus. Self-administration within operant conditioning is a valid model to investigate drug-seeking and drug-taking behaviour in rats. Cannabinoid CB1 receptors are involved in reinstatement of alcohol-seeking behaviour and of many other drugs of abuse (3). Accordingly, this study was aimed at the evaluation of: 1) the motivational properties of oral ACD in the induction and maintenance of an operant-drinking behaviour; 2) the onset of a relapse drinking behaviour, following ACD deprivation; 3) ACD effect in a conflict situation employing the …

ETHANOL PREFERENCE DURING PREGNANCY AFTER LONG-TERM ETHANOL CONSUMPTION: EFFECT OF DRINKING PATTERN AND MATERNAL BEHAVIOUR ANALYSIS

Several studies suggest that pregnancy can reduce ethanol preference and consumption in rats and mice when self-administration starts early during pregnancy (Randall et al., 1980; Means and Goy, 1982). Our first aim was to explore the effect of pregnancy on long-term habit to ethanol, in female rats subjected to 12-week continuous or intermittent (3 days/week) access to 20% ethanol; they were named CARs and IARs respectively. The second aim was to observe their maternal behaviour. Rats were deprived from ethanol during mating and the first gestational week, and then re-exposed to respective ethanol self-administration schedule, starting from the second week of pregnancy. Maternal behaviour …

PHARMACOLOGICAL MODULATION OF OPERANT BEHAVIOUR FOR ACETALDEHYDE. INVOLVEMENT OF D2 AND CB1 RECEPTORS.

Acetaldehyde (ACD), the first metabolite of ethanol, has rewarding and motivational properties, as shown by behavioural studies specifically tailored for studying addictive-like behaviour (1, 2). The rewarding and incentive effects of alcohol and others addictive substances, result from their capability to enhance mesolimbic dopamine (DA) transmission, as well as to affect the cannabinoid system, which is able to fine-tune the activity of DA neurons (3). ACD directly increases DA neurotransmission (4), but the neural underpinning the operant behaviour for oral-self administered ACD still remains poorly understood. Since D2 and CB1 receptors are involved in alcohol addiction (3), as well as …

Acetaldehyde operant self-administration in rats: focus on D2-receptor activation.

Acetaldehyde (ACD), ethanol first metabolite, is rewarding in rodents and humans; it induces “place preference”, is self-administer directly in the VTA, orally in an operant/conflict paradigm and increases DA neurons’ firing. This research aims at investigating DA2-receptor role in the reinstatement of acetaldehyde operant-drinking behaviour, following induction, maintenance and abstinence in the rat. Male Wistar rats are trained to orally self-administer ACD solution (3.2% v/v) or water, in an operant chamber under a FR1. Afterwards animals undergo cyclic periods of deprivation and relapse to ACD. The effect ofD2-receptor activation by quinpirole (0.03mg/kg,i.p.) on operant ACD self-admini…

Gender-specific vulnerability to alcohol and depression. Focus on glutamatergic synapses in the nucleus accumbens

Is Acetaldehyde a substance of abuse? Evidence from a free-access, three-bottle choice paradigm

At present, neuroscience literature dealing with Acetaldehyde (ACD), ethanol first metabolite, as a drug of abuse, reported conditioned taste aversion paradigm and conditioned place preference, following ICV or i.p. administration. No reports exist on ACD oral self-administration probably because of its high volatility. For this reason, this pilot study was aimed at the evaluation of ACD concentration in aqueous solutions, and consequently to the rat drinking behaviour when acetaldehyde was presented in a free-access paradigm together with water and a sweet solution. Preliminarly we investigated the loss of ACD content in aqueous standard solutions. For the investigation of ACD concentratio…

Neuromodulatory effect of interleukin 1β in the dorsal raphe nucleus on individual differences in aggression

Heightened aggressive behavior is considered as one of the central symptoms of many neuropsychiatric disorders including autism, schizophrenia, and dementia. The consequences of aggression pose a heavy burden on patient’s families, clinicians, and the patients themselves. At the same time, we have limited treatment options for aggression and lack mechanistic insight into the causes of aggression needed to inform new efforts in drug discovery and development. Levels of proinflammatory cytokines in the periphery or cerebrospinal fluid were previously reported to correlate with aggressive traits in humans. However, it is still unknown whether cytokines affect brain circuits to modulate aggress…

Adolescent binge-like alcohol exposure dysregulates NPY and CGRP in rats: Behavioural and immunochemical evidence.

Alcohol binge drinking during adolescence impacts affective behaviour, possibly impinging on developing neural substrates processing affective states, including calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY). Here, we modelled binge-like alcohol exposure in adolescence, by administering 3.5 g/kg alcohol per os, within 1 h time, to male adolescent rats every other day, from postnatal day 35 to 54. The effects on positive and negative affective behaviour during abstinence were explored, including consummatory behaviour and weight gain; social behaviour in the modified social interaction test; thermal nociception in the tail-flick test; psychosocial stress coping in the reside…

Detection of a temporal structure in the rat behavioural response to an aversive stimulation in the emotional object recognition (EOR) task.

Abstract Aim of the research was to investigate whether a temporal structure could be detected in the behavioural response to an aversive stimulation. A fear-related memory task was used in rats, placed in a modified version of the Novel Object Recognition task known as Emotional Object Recognition task, i.e. a behavioural assay that orbits around the declarative memory for an aversive experience. To this purpose, twelve male Wistar rats, divided in two groups (Control and Aversive memory), observed after 4 h (OR4h) and after 24 h (OR24h) from the delivery of an aversive stimulation, associated to a specific object, were used. Data were evaluated both in terms of conventional quantitative a…

Alcohol binge drinking in adolescence and psychological profile: Can the preclinical model crack the chicken-or-egg question?

During adolescence, internal and external factors contribute to engaging with alcohol binge drinking (ABD), putting at risk the neurodevelopment of brain regions crucial for emotional control and stress coping. This research assessed the prevalence of ABD in late adolescent students of Southern Italy and characterized their psychological profile and drinking motives. Translational effects of alcohol binge drinking in the animal model were also studied. Seven hundred and fifty-nine high school students of both sexes (aged 18–20) were recruited. Alcohol Use Disorder Identification Test-Consumption (AUDIT-C), Drinking Motives Questionnaire-Revised Short Form, Millon Clinical Multiaxial Invento…

SY26-2ACETALDEHYDE ENDOCANNABINOIDS AND DOPAMINE: IS THIS –JUST- “A MENAGE A TROIS”?

As ethanol, its first metabolite, acetaldehyde (ACD), enhances dopamine neurotransmission and exerts rewarding and motivational effects in animal models tailored for studying addictive-like behaviours. The endocannabinoid system fine-tuning dopamine cell activity, affects distinct drug-related behaviours and specific drug-induced effects. In light of this, it becomes urgent to investigate the implications of …

Patterns matter: continuous Vs intermittent access to ethanol differently affects withdrawal behavioural phenotype and maternal care in female rats.

Modeling voluntary ethanol consumption in female rats is crucial for gaining further insight in gender-related vulnerability to alcohol. Since ethanol effects depend not only on the amount consumed, but also on drinking pattern, this study aimed at assessing the influence of continuous and intermittent ethanol self-administration on peculiar aspects of female behavioural repertoire during withdrawal and relapse. Female rats undergoing a 15-week-long, 20% ethanol continuous or intermittent (3days/week) access, respectively named CARs and IARs, were tested for alcohol intake (gr/kg) and preference. During withdrawal we assessed: novelty and reward preference in novel object exploration and sa…

EFFECT OF ACETALDEHYDE INTOXICATION AND WITHDRAWAL ON NEUROPEPTIDE Y EXPRESSION. FOCUS ON CB1 RECEPTOR ROLE.

Neuropeptide Y (NPY) acts as an endogenous anxiolytic, and, like endocannabinoids, plays an important role in the regulation of neuronal excitability during ethanol withdrawal (Rubio et al., 2011). Since acetaldehyde is considered a mediator of ethanol central effects, this research aims at investigating, following intoxication and during withdrawal, the effects of acetaldehyde on NPY expression in brain areas particularly vulnerable to alcohol, and the influence of cannabinoid system on it. Rats underwent acetaldehyde intoxication (450mg/kg, i.g., 4 times daily for 4 days); AM281, a CB1 selective antagonist (2,5 mg/kg, i.p.) was administered during abstinence. Immunohistochemical analysis …

Vulnerability to alcohol operant-drinking behaviour: implications of environmental stim

Environmental stimuli, occurring early in life, shape the drinking trajectories and the psychopathological outcome of alcohol consumption in adult life. In particular, early perinatal procedures can permanently alter various patterns of drug use and behaviour in rat adulthood (Pryce CR, 2001). Early handling (EH) apparently is responsible for neurochemical and behavioural changes in adulthood, due to boosts in maternal care after daily reunion. It has been suggested that fostered maternal care, in the form of licking and grooming, is a key feature in determining neural changes and offspring fear responses and alter the reward/reinforcement pathway through epigenetic mechanisms that likely u…

Increased functional connectivity in gambling disorder correlates with behavioural and emotional dysregulation: Evidence of a role for the cerebellum

Gambling disorder (GD) is a psychiatric disease that has been recently classified as a behavioural addiction. So far, a very few studies have investigated the alteration of functional connectivity in GD patients, thus the concrete interplay between relevant function-dependent circuitries in such disease has not been comprehensively assessed. The aim of this research was to investigate resting-state functional connectivity in GD patients, searching for a correlation with GD symptoms severity. GD patients were assessed for gambling behaviour, impulsivity, cognitive distortions, anxiety and depression, in comparison with healthy controls (HC). Afterwards, they were assessed for resting-state f…

Targeting the Stress System During Gestation: Is Early Handling a Protective Strategy for the Offspring?

The perinatal window is a critical developmental time when abnormal gestational stimuli may alter the development of the stress system that, in turn, influences behavioral and physiological responses in the newborns. Individual differences in stress reactivity are also determined by variations in maternal care, resulting from environmental manipulations. Despite glucocorticoids are the primary programming factor for the offspring's stress response, therapeutic corticosteroids are commonly used during late gestation to prevent preterm negative outcomes, exposing the offspring to potentially aberrant stress reactivity later in life. Thus, in this study, we investigated the consequences of one…

Environmental enrichment reverts the effects of continuous or intermittent perinatal alcohol exposure. Focus on alcohol vulnerability and affectivity in the offspring

Alcohol consumption during perinatal periods is common, despite the warning of adverse effects on the foetal development. In female rats, the intermittent pattern of alcohol consumption is responsible for higher drinking levels and more profound disruption of maternal care than traditional continuous free-access paradigm, which can have persistent effects on the offspring. The environmental enrichment, a powerful form of experience-dependent plasticity that allows high cognitive, motor and sensory stimulations, is helpful for recovering from different neurological pathologies. Thus, this study aimed at exploring the effects of environmental enrichment on alcohol vulnerability and affective …

Environmental Enrichment During Adolescence Mitigates Cognitive Deficits and Alcohol Vulnerability due to Continuous and Intermittent Perinatal Alcohol Exposure in Adult Rats.

Perinatal alcohol exposure affects ontogenic neurodevelopment, causing physical and functional long-term abnormalities with limited treatment options. This study investigated long-term consequences of continuous and intermittent maternal alcohol drinking on behavioral readouts of cognitive function and alcohol vulnerability in the offspring. The effects of environmental enrichment (EE) during adolescence were also evaluated. Female rats underwent continuous alcohol drinking (CAD)—or intermittent alcohol drinking paradigm (IAD), along pregestation, gestation, and lactation periods—equivalent to the whole gestational period in humans. Male offspring were reared in standard conditions or EE un…

Dopamine involvement in Acetaldehyde drinking behaviour: role of Ropinirole on.

Rats self-administer acetaldehyde(ACD), ethanol's first metabolite, directly into cerebral ventricles (1), and multiple ICV infusions of ACD produce conditioned place preference (2). ACD, such as alcohol and other substances of abuse, interacts with dopaminergic reward system (3) and its reinforcing and addictive properties have been assessed through an operant-conflict conditioning procedure (4). Since dopamine D2receptor over-expression in the Nacc attenuates alcohol intake (5), this study aims at exploring the effects of ropinirole administration during abstinence, on ACD relapse. The protocol has been scheduled into 3 different periods: training ( animals have been trained to self-admin…

Psychological assessment in pathological gamblers treated with escitalopram

Pathological Gambling (PG) is classified as a "Disorder of Impulse Control", but due to similarities with drug addiction is frequently described as a drug-free addiction (Potenza et al., 2012). PG is conceptualized as a behavioural addiction because of its neurobiologic, neurophysiologic and psychological features. Current therapeutical approaches seem unsatisfactory as they do not achieve definitive positive outcomes. Considering the well known psycopathological comorbidities, PG represents both a social (impact on relatives money/life) and a sanitary cost, in terms of pharmacological and psychological support. The compulsive behaviour detectable in PG, is a disease with neurophysiopatholo…

Social stress under binge-like alcohol withdrawal in adolescence: evidence of cannabidiol effect on maladaptive plasticity in rats.

Abstract Background Alcohol binge drinking may compromise the functioning of the nucleus accumbens (NAc), i.e. the neural hub for processing reward and aversive responses. Methods As socially stressful events pose particular challenges at developmental stages, this research applied the resident–intruder paradigm as a model of social stress, to highlight behavioural neuroendocrine and molecular maladaptive plasticity in rats at withdrawal from binge-like alcohol exposure in adolescence. In search of a rescue agent, cannabidiol (CBD) was selected due to its favourable effects on alcohol- and stress-related harms. Results Binge-like alcohol exposed intruder rats displayed a compromised defensi…