Dehydroepiandrosterone (DHEA) attenuates cocaine-seeking behavior in the self-administration model in rats

Recent studies have emphasized the role of the maternal diet in the development of mental disorders in offspring. Substance use disorder is a major global health and economic burden. Therefore, the search for predisposing factors for the development of this disease can contribute to reducing the health and social damage associated with addiction. In this study, we focused on the impact of the maternal diet on changes in melanocortin-4 (MC-4) receptors as well as on behavioral changes related to cocaine addiction. Rat dams consumed a high-fat diet (HFD), high-sugar diet (HSD, rich in sucrose), or mixed diet (MD) during pregnancy and lactation. Using an intravenous cocaine self-administration model, the susceptibility of female offspring to cocaine reward and cocaine-seeking propensities was evaluated. In addition, the level of MC-4 receptors in the rat brain structures related to cocaine reward and relapse was assessed. Modified maternal diets did not affect cocaine self-administration in offspring. However, the maternal HSD enhanced cocaine-seeking behavior in female offspring. In addition, we observed that the maternal HSD and MD led to increased expression of MC-4 receptors in the nucleus accumbens, while increased MC-4 receptor levels in the dorsal striatum were observed after exposure to the maternal HSD and HFD. Taken together, it can be concluded that a maternal HSD is an important factor that triggers cocaine-seeking behavior in female offspring and the expression of MC-4 receptors.

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Fos Protein Expression and Cocaine-Seeking Behavior in Rats after Exposure to a Cocaine Self-Administration Environment

Journal of Neuroscience ◽

10.1523/jneurosci.20-02-00798.2000 ◽

2000 ◽

Vol 20 (2) ◽

pp. 798-805 ◽

Cited By ~ 297

Author(s):

Janet L. Neisewander ◽

David A. Baker ◽

Rita A. Fuchs ◽

Ly T. L. Tran-Nguyen ◽

Art Palmer ◽

...

Keyword(s):

Protein Expression ◽

Self Administration ◽

Fos Protein ◽

Cocaine Seeking ◽

Seeking Behavior

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Inactivation of NMDA Receptors in the Ventral Tegmental Area during Cocaine Self-Administration Prevents GluA1 Upregulation but with Paradoxical Increases in Cocaine-Seeking Behavior

Journal of Neuroscience ◽

10.1523/jneurosci.2828-16.2017 ◽

2017 ◽

Vol 38 (3) ◽

pp. 575-585 ◽

Cited By ~ 6

Author(s):

Daniel Guzman ◽

Maria B. Carreira ◽

Allyson K. Friedman ◽

Megumi Adachi ◽

Rachael L. Neve ◽

...

Keyword(s):

Nmda Receptors ◽

Ventral Tegmental Area ◽

Self Administration ◽

Cocaine Seeking ◽

Seeking Behavior ◽

Ventral Tegmental

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Disrupting Reconsolidation by Systemic Inhibition of mTOR Kinase via Rapamycin Reduces Cocaine-Seeking Behavior

Frontiers in Pharmacology ◽

10.3389/fphar.2021.652865 ◽

2021 ◽

Vol 12 ◽

Author(s):

Fushen Zhang ◽

Shihao Huang ◽

Haiyan Bu ◽

Yu Zhou ◽

Lixiang Chen ◽

...

Keyword(s):

Spontaneous Recovery ◽

Time Window ◽

Mammalian Target Of Rapamycin ◽

Self Administration ◽

Mtor Inhibition ◽

Cocaine Seeking ◽

Seeking Behavior ◽

Previously Treated ◽

Cocaine Infusion ◽

Paired Tone

Drug addiction is considered maladaptive learning, and drug-related memories aroused by the presence of drug related stimuli (drug context or drug-associated cues) promote recurring craving and reinstatement of drug seeking. The mammalian target of rapamycin signaling pathway is involved in reconsolidation of drug memories in conditioned place preference and alcohol self-administration (SA) paradigms. Here, we explored the effect of mTOR inhibition on reconsolidation of addiction memory using cocaine self-administration paradigm. Rats received intravenous cocaine self-administration training for 10 consecutive days, during which a light/tone conditioned stimulus was paired with each cocaine infusion. After acquisition of the stable cocaine self-administration behaviors, rats were subjected to nosepoke extinction (11 days) to extinguish their behaviors, and then received a 15 min retrieval trial with or without the cocaine-paired tone/light cue delivery or without. Immediately or 6 h after the retrieval trial, rapamycin (10 mg/kg) was administered intraperitoneally. Finally, cue-induced reinstatement, cocaine-priming-induced reinstatement and spontaneous recovery of cocaine-seeking behaviors were assessed in rapamycin previously treated animals, respectively. We found that rapamycin treatment immediately after a retrieval trial decreased subsequent reinstatement of cocaine seeking induced by cues or cocaine itself, and these effects lasted at least for 28 days. In contrast, delayed intraperitoneal injection of rapamycin 6 h after retrieval or rapamycin injection without retrieval had no effects on cocaine-seeking behaviors. These findings indicated that mTOR inhibition within the reconsolidation time-window impairs the reconsolidation of cocaine associated memory, reduces cocaine-seeking behavior and prevents relapse, and these effects are retrieval-dependent and temporal-specific.

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Cannabidiol effects on cocaine-seeking behaviour and incubation of craving in mice

10.1101/2020.12.18.423391 ◽

2020 ◽

Author(s):

Laia Alegre-Zurano ◽

Miguel Á. Luján ◽

Lídia Cantacorps ◽

Ana Martín-Sánchez ◽

Alba García-Baos ◽

...

Keyword(s):

Economic Analysis ◽

Ventral Striatum ◽

The Self ◽

List Type ◽

Self Administration ◽

Demand Curves ◽

Cocaine Seeking ◽

Cocaine Craving ◽

Behavioural Economic ◽

Incubation Of Craving

ABSTRACTBackground and PurposeTo remain abstinent represents one of the major challenges for the treatment of cocaine use disorder. Cocaine seeking elicited by drug-associated cues progressively intensifies during abstinence in a process termed incubation of craving, representing an aggravating factor for relapse. Cannabidiol is a phytocannabinoid that exerts protecting effects upon cocaine-seeking behaviour, although its effects on cocaine-craving incubation have never been elucidated.Experimental ApproachWe developed a mouse model of behavioural economic analysis of demand curves and incubation of cue-induced cocaine craving. Changes in the protein expression of AMPAR subunits and ERK1/2 phosphorylation were analysed. We also assessed the effects of cannabidiol (20 mg·kg-1) administered either during acquisition of cocaine self-administration or abstinence.Key ResultsMice efficiently performed the demand task and incubation of cocaine craving. Besides, changes in GluA1 and GluA2 protein levels were found along the abstinence in prelimbic cortex, ventral striatum and amygdala, as well as a decrease in ERK1/2 phosphorylation in ventral striatum. Cannabidiol reduced ongoing cocaine intake when administered during the acquisition phase of the self-administration, but failed to alter the subsequent demand task performance and incubation of cocaine craving. No effects were found when cannabidiol was administered during the abstinence period.Conclusion and ImplicationsWe provide here a novel model of behavioural economic analysis of demand curves and cue-induced incubation of cocaine-seeking behaviour for mice. Moreover, we show that cannabidiol exerts differential effects on the current model depending on the self-administration phase in which it was administered.What is already knownBehavioural economics and incubation of cocaine craving are well-stablished paradigms to evaluate cocaine seeking in rats.CBD reduces cocaine-seeking and cocaine-taking behaviours.What this study addsA mouse model of behavioural economic analysis of demand curves and incubation of cue-induced cocaine craving.CBD reduces cocaine self-administration and has no effect over demand task and cocaine-craving incubation.Clinical significanceA new behavioural model for studying cocaine addiction in mice.CBD exerts differential effects depending on when it was administered in the addictive process.Tables of Links

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