0000000000201518
AUTHOR
Concepción Roger-sánchez
showing 16 related works from this author
Pharmacological modulation of protein kinases as a new approach to treat addiction to cocaine and opiates.
2016
Drug addiction shares brain mechanisms and molecular substrates with learning and memory processes, such as the stimulation of glutamate receptors and their downstream signalling pathways. In the present work we provide an up-to-date review of studies that have demonstrated the implication of the main memory-related calcium-dependent protein kinases in opiate and cocaine addiction. The effects of these drugs of abuse in different animal models of drug reward, dependence and addiction are altered by manipulation of the mitogen-activated protein kinase (MAPK) family, particularly extracellular signal regulated kinase (ERK), calcium/calmodulin-dependent kinase II (CaMKII), the protein kinase C…
Role of the nNOS gene in ethanol-induced conditioned place preference in mice
2009
Nitric oxide (NO) produced by neuronal nitric oxide synthase (nNOS) has a role in synaptic plasticity, and evidence suggests its role in a range of effects produced by alcohol in the central nervous system. The aim of the current study was to investigate the role of the nNOS gene in the development of ethanol-induced conditioned place preference (CPP) in mice. The CPP paradigm is designed to investigate the reinforcing properties of drugs of abuse and the development of maladaptive behaviors, such as conditioned response to drug-associated stimuli, following repeated drug exposure. Adult male and female wild type (WT) and nNOS knockout (KO) mice on a mixed B6; 129S genetic background were t…
Role of dopamine neurotransmission in the long-term effects of repeated social defeat on the conditioned rewarding effects of cocaine
2016
Numerous studies report that social defeat stress alters dopamine (DA) neurotransmission in several areas of the brain. Alterations of the mesolimbic dopaminergic pathway are believed to be responsible for the increased vulnerability to drug use observed as a result of social stress. In the present study, we evaluated the influence of DA receptors on the long-term effect of repeated social defeat (RSD) on the conditioned rewarding and reinstating effects of cocaine. For this purpose, the D1R antagonist SCH 23390 and the D1R antagonist raclopride were administered 30 min before each social defeat and a cocaine-induced CPP procedure was initiated three weeks later. The expression of the D1R a…
Effect of adolescent exposure to WIN 55212-2 on the acquisition and reinstatement of MDMA-induced conditioned place preference.
2009
The present study employs a conditioned place preference procedure (CPP) to examine the effects of exposure to the cannabinoid agonist WIN 55212-2 (WIN) (0.1 and 0.5mg/kg) during adolescence on the reinforcing properties of +/-3,4-methylenedioxymetamphetamine hydrochloride (MDMA) (1.25 and 2.5mg/kg) in mice. On postnatal day (PD) 27, animals received a daily injection of the assigned treatment on 5 consecutive days, and three days later the place conditioning procedure was initiated (PD 35). The results suggest that pre-exposure to cannabinoids strengthens the properties of MDMA and favors reinstatement of the craving for the drug, which endorses the gateway hypothesis.
Role of the dopaminergic system in the acquisition, expression and reinstatement of MDMA-induced conditioned place preference in adolescent mice.
2012
Background The rewarding effects of 3,4-methylenedioxy-metamphetamine (MDMA) have been demonstrated in conditioned place preference (CPP) procedures, but the involvement of the dopaminergic system in MDMA-induced CPP and reinstatement is poorly understood. Methodology/Principal Findings In this study, the effects of the DA D1 antagonist SCH 23390 (0.125 and 0.250 mg/kg), the DA D2 antagonist Haloperidol (0.1 and 0.2 mg/kg), the D2 antagonist Raclopride (0.3 and 0.6 mg/kg) and the dopamine release inhibitor CGS 10746B (3 and 10 mg/kg) on the acquisition, expression and reinstatement of a CPP induced by 10 mg/kg of MDMA were evaluated in adolescent mice. As expected, MDMA significantly increa…
'Up-regulation of histone acetylation induced by social defeat mediates the conditioned rewarding effects of cocaine
2016
Social defeat (SD) induces a long-lasting increase in the rewarding effects of psychostimulants measured using the self-administration and conditioned place procedures (CPP). However, little is known about the epigenetic changes induced by social stress and about their role in the increased response to the rewarding effects of psychostimulants. Considering that histone acetylation regulates transcriptional activity and contributes to drug-induced behavioral changes, we addressed the hypothesis that SD induces transcriptional changes by histone modifications associated with the acquisition of place conditioning. After a fourth defeat, H3(K9) acetylation was decreased in the hippocampus, whil…
Discrimination between cocaine-associated context and cue in a modified conditioned place preference paradigm: role of the nNOS gene in cue condition…
2009
The conditioned place preference (CPP) paradigm entails appetitive learning and is utilized to investigate the motivational effects of drug and natural reward in rodents. However, a typical CPP design does not allow dissociation between cue- and context-dependent appetitive learning. In humans, context and cues that had been associated with drug reward can elicit conditioned response and drug craving. Therefore, we investigated (a) methods by which to discriminate between cue- and context-dependent appetitive learning, and (b) the role of the neuronal nitric oxide synthase (nNOS) gene in appetitive learning. Wild-type (WT) and nNOS knockout (KO) mice were trained by cocaine (20 mg/kg) in a …
Neurochemical Substrates of MDMA Reward: Effects of the Inhibition of Serotonin Reuptake on the Acquisition and Reinstatement of MDMA-induced CPP
2013
Different neurotransmitter brain systems have been implicated in the rewarding effects of 3,4-methylenedioxymetamphetamine (MDMA), including dopamine or serotonin. Serotonin selective reuptake inhibitors (SSRI) are a commonly prescribed therapy for psychiatric disorders, and the SSRI fluoxetine is recommended for MDMA users due to its neuroprotective effect against MDMAinduced neurotoxicity. In the present work, we employed the conditioned place preference (CPP) paradigm to study how the inhibition of serotonin reuptake with fluoxetine affected the rewarding and reinstating effects of MDMA in adolescent male mice. Firstly, we evaluated the motivational effects of fluoxetine (1 and 10 mg/kg)…
Dopamine D2 receptors mediate the increase in reinstatement of the conditioned rewarding effects of cocaine induced by acute social defeat
2017
Social stress modifies the activity of brain areas involved in the rewarding effects of psychostimulants, inducing neuroadaptations in the dopaminergic mesolimbic system and modifying the sensitivity of dopamine receptors. In the present study we evaluated the effect of the dopamine D1- and D2-like receptor antagonists (SCH23390 and raclopride, respectively) on the short-time effects of acute social defeat (ASD). Male OF1 mice were socially defeated before each conditioning session of the conditioned place preference (CPP) induced by 1mg/kg or 25mg/kg of cocaine plus the corresponding dopamine antagonist. A final experiment was designed to evaluate the effect of the dopamine antagonists on …
Involvement of 5-hydroxytryptamine 5-HT3 serotonergic receptors in the acquisition and reinstatement of the conditioned place preference induced by M…
2013
Some MDMA (3,4-methylenedioxymethamphetamine) users develop dependence as a result of chronic consumption. The present study evaluated the role of 5-hydroxytryptamine 5-HT₃ receptors in the acquisition, expression and reinstatement of the conditioned place preference (CPP) induced by MDMA. Adolescent male mice were conditioned with 10 mg/kg of MDMA and then treated with 1 or 3mg/kg of the 5-hydroxytryptamine 5-HT₃ antagonist MDL72222 during acquisition of conditioning (experiment 1), before expression of CPP in a post-conditioning test (experiment 2) or before a reinstatement test (experiment 3). MDL72222 was devoid of motivational effects but blocked acquisition of the MDMA-induced CPP. Mo…
Cocaine enhances the conditioned rewarding effects of MDMA in adolescent mice.
2015
Although the consumption of cocaine is frequent in young users of MDMA (3,4-methylenedioxymethamphetamine), the influence of exposure to cocaine on the rewarding effects of MDMA in adolescents has not been studied. The purpose of the present work was to evaluate the effect of co-administration of cocaine (1 and 10 mg/kg) and a sub-threshold dose of MDMA (1.25 mg/kg) on the acquisition of conditioned place preference (CPP) (experiment 1). In addition, the effect of pre-treatment with cocaine on MDMA-induced CPP was evaluated (experiment 2). Levels of monoamines in striatum, hippocampus and cortex were measured in both experiments. Our hypotheses were that cocaine co-administration or pre-tre…
Cognitive and behavioural effects induced by social stress plus MDMA administration in mice
2017
Adverse life experiences such as social stress may make an individual more vulnerable to drug addiction and mental disorders associated with drug consumption. The present work aimed to evaluate the effects of stress induced by acute social defeat combined with the administration of 3,4-methylenedioxymethamphetamine (MDMA) on depression-like behaviour, memory function and motor response to drug in late adolescent male mice. Two groups of mice were exposed to social defeat (SD) during four encounters with an aggressive co-specific, which took place on alternate days. Immediately after defeat, animals were treated with saline or MDMA 10mg/kg (SD+SAL and SD+MDMA). In control groups, mice were p…
Effects of risperidone on the acquisition and reinstatement of the conditioned place preference induced by MDMA
2013
Some users of 3,4-methylenedioxymethylamphetamine (MDMA or ecstasy) abuse this drug and/or become concerned about their use. These individuals would benefit greatly from the development of pharmacological strategies to reduce MDMA consumption. We have previously observed that antipsychotics block acquisition and expression of the conditioned place preference (CPP) induced by MDMA, though they do not modify priming-induced reinstatement of MDMA-induced CPP after extinction. In the present study we have evaluated the capacity of the mixed serotonin (5-HT2A)/dopamine (DA D2) antagonist risperidone to block acquisition and reinstatement of MDMA induced-CPP. Adolescent male mice conditioned with…
Effects of Cannabinoid Exposure during Adolescence on the Conditioned Rewarding Effects of WIN 55212-2 and Cocaine in Mice: Influence of the Novelty-…
2016
Adolescent exposure to cannabinoids enhances the behavioural effects of cocaine, and high novelty-seeking trait predicts greater sensitivity to the conditioned place preference (CPP) induced by this drug. Our aim was to evaluate the influence of novelty-seeking on the effects of adolescent cannabinoid exposure. Adolescent male mice were classified as high or low novelty seekers (HNS and LNS) in the hole-board test. First, we evaluated the CPP induced by the cannabinoid agonist WIN 55212-2 (0.05 and 0.075 mg/kg, i.p.) in HNS and LNS mice. Then, HNS and LNS mice were pretreated i.p. with vehicle, WIN 55212-2 (0.1 mg/kg), or cannabinoid antagonist rimonabant (1 mg/kg) and were subsequently con…
Age- and sex-related differences in the acquisition and reinstatement of ethanol CPP in mice
2011
Many people begin to experiment with alcohol during adolescence, an important developmental period during which sex differences in the effects of ethanol appear. In the present study we evaluated the effect of ethanol (0, 0.625, 1.25 or 2.5 g/kg) on the acquisition of a conditioned place preference (CPP) in early and late adolescent male and female mice. In addition, we assessed the capacity of ethanol to induce reinstatement of the CPP after its extinction. CPP was induced in early and late adolescent females with 2.5 g/kg, and in early adolescent males with 1.25 or 2.5 g/kg of ethanol. No CPP was observed in late adolescent males. Priming with ethanol reinstated the CPP induced by the hig…
Neurochemical substrates of the rewarding effects of MDMA: implications for the development of pharmacotherapies to MDMA dependence.
2015
In recent years, studies with animal models of reward, such as the intracranial self-stimulation, self-administration, and conditioned place preference paradigms, have increased our knowledge on the neurochemical substrates of the rewarding effects of 3,4-methylenedioxymetamphetamine (MDMA) in rodents. However, pharmacological and neuroimaging studies with human participants are scarce. Serotonin [5-hydroxytryptamine (5-HT)], dopamine (DA), endocannabinoids, and endogenous opiates are the main neurotransmitter systems involved in the rewarding effects of MDMA in rodents, but other neurotransmitters such as glutamate, acetylcholine, adenosine, and neurotensin are also involved. The most impo…