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…

Alcohol abuse and insomnia disorder: Focus on a group of night and day workers

The sleep-wake cycle plays a fundamental role in maintaining the physiological balance of our body. Its alteration favours the genesis of several organic alterations and diseases including sleep disorders and the consumption of several substances of abuse. It has been reported that the work activity, especially that carried out during the night, is able to influence the sleep-wake cycle, promoting the development of insomnia, which, in turn, would subject the worker to a stressful condition such as to encourage adverse behaviour such as the use/abuse of psychotropic substances. Based on the above premises, the aim of our research was to evaluate, in night workers: (i) the pattern of consump…

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

IN-UTERO Δ9-TETRAHYDROCANNABINOL EXPOSURE IMPINGES ON BRAIN EXECUTIVE PROCESSES TOWARDS EMOTIONAL, COGNITIVE IMPAIRMENT, AND ALCOHOL VULNERABILITY IN THE RAT OFFSPRING: BEHAVIORAL AND NEUROCHEMICAL EVIDENCE

Alcohol and Nicotine Use among Adolescents: An Observational Study in a Sicilian Cohort of High School Students

In recent years, the mode of alcoholic intake known as binge drinking (BD) has become a common practice, especially among adolescents who, due to socio-environmental motives, tend to reach a rapid state of drunkenness. This drunkeness leads to alterations in brain areas responsible for executive functions and cognitive processes, as well as to the genesis of factors that predispose to lasting addiction. Likewise, nicotine leads to a comparable degree of addiction. On this basis, the aim of this research was to evaluate, on a cohort of 349 high school students (15–17 years old) in the province of Palermo, the following: (I) the drinking model of alcoholic beverages; (II) the use of nic…

The endocannabinoid-alcohol crosstalk: Recent advances on a bi-faceted target

Increasing evidence has focusesed on the endocannabinoid system as a relevant player in the induction of aberrant synaptic plasticity and related addictive phenotype following chronic excessive alcohol drinking. In addition, the endocannabinoid system is implicated in the pathogenesis of alcoholic liver disease. Interestingly, whereas the involvement of CB1 receptors in alcohol rewarding properties is established, the central and peripheral action of CB2 signalling is still to be elucidated. This review aims at giving the input to deepen knowledge on the role of the endocannabinoid system, highlighting the advancing evidence that suggests that CB1 and CB2 receptors may play opposite roles i…

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…

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…

In utero Δ9-tetrahydrocannabinol exposure confers vulnerability towards cognitive impairments and alcohol drinking in the adolescent offspring: Is there a role for neuropeptide Y?

Background:Cannabinoid consumption during pregnancy has been increasing on the wave of the broad-based legalisation of cannabis in Western countries, raising concern about the putative detrimental outcomes on foetal neurodevelopment. Indeed, since the endocannabinoid system regulates synaptic plasticity, emotional and cognitive processes from early stages of life interfering with it and other excitability endogenous modulators, such as neuropeptide Y (NPY), might contribute to the occurrence of a vulnerable phenotype later in life.Aims:This research investigated whether in utero exposure to Δ9-tetrahydrocannabinol (THC) may induce deficits in emotional/cognitive processes and alcohol vulner…

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…

Pre-conceptional and Peri-Gestational Maternal Binge Alcohol Drinking Produces Inheritance of Mood Disturbances and Alcohol Vulnerability in the Adolescent Offspring

Although binge drinking is on the rise in women of reproductive age and during pregnancy, the consequences in the offspring, in particular the inheritance of alcohol-related mood disturbances and alcohol abuse vulnerability, are still poorly investigated. In this study, we modeled both Habitual- and Binge Alcohol Drinking (HAD and BAD) in female rats by employing a two-bottle choice paradigm, with 20% alcohol and water. The exposure started 12 weeks before pregnancy and continued during gestation and lactation. The consequences induced by the two alcohol drinking patterns in female rats were assessed before conception in terms of behavioral reactivity, anxiety- and depressive-like behavior.…

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…

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…

Homer2 and alcohol: A mutual interaction

The past two decades of data derived from addicted individuals and preclinical animal models of addiction implicate a role for the excitatory glutamatergic transmission within the mesolimbic structures in alcoholism. The cellular localization of the glutamatergic receptor subtypes, as well as their signaling efficiency and function, are highly dependent upon discrete functional constituents of the postsynaptic density, including the Homer family of scaffolding proteins. The consequences of repeated alcohol administration on the expression of the Homer family proteins demonstrate a crucial and active role, particularly for the expression of Homer2 isoform, in regulating alcohol-induced behav…