Conditioned Place Preference (CPP) in Rats: From Conditioning to Reinstatement Test

Patients with psychiatric disorders, such as gambling and substance use, tend to exhibit maladaptive decision-making. In this study, we assessed individual differences in risk-taking behaviors using a rat gambling task (GT) and investigated the relationship between risk-taking behaviors and vulnerability to drug dependence using methamphetamine (METH)-induced conditioned place preference (CPP). In the GT using a radial arm maze, male Long-Evans rats were trained to choose one of three choice arms (a low-risk/low-reward (L-L), a high-risk/high-reward (H-H), and an empty arm) in 16 trials per day for 14 days. METH-induced CPP consisted of 6 sessions: habituation, conditioning, preference test (Test I), extinction, extinction test (Test II), and reinstatement test (Test III). Results demonstrated that the percentage of choosing the H-H arm was significantly positively correlated with the preference score for the METH-paired compartment in the preference test, but not with the extinction and reinstatement tests, suggesting that risk-taking rats are more vulnerable to drug dependence.

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Cannabidiol prevents priming- and stress-induced reinstatement of the conditioned place preference induced by cocaine in mice

Journal of Psychopharmacology ◽

10.1177/0269881120965952 ◽

2021 ◽

pp. 026988112096595

Author(s):

Claudia Calpe-López ◽

Ani Gasparyan ◽

Francisco Navarrete ◽

Jorge Manzanares ◽

Jose Miñarro ◽

...

Keyword(s):

Gene Expression ◽

Ventral Tegmental Area ◽

Conditioned Place Preference ◽

Cannabis Sativa ◽

Social Defeat ◽

Place Preference ◽

Cocaine Seeking ◽

Ventral Tegmental ◽

Relative Gene ◽

Reinstatement Test

Background: Cocaine dependence is an important problem without any effective pharmacological treatment. Some preclinical studies have suggested that cannabidiol (CBD), a component of the Cannabis sativa plant, could be useful for the treatment of cocaine use disorders. Aims: This work aims to evaluate the ability of CBD to reduce priming- and stress-induced reinstatement of the conditioned place preference (CPP) induced by cocaine. Methods: Young adult CD-1 male mice were allocated to 10 groups ( n = 12/group), conditioned with cocaine (10 mg/kg) and exposed to extinction of CPP (two sessions per week). When extinction was achieved, each group received the corresponding treatment before the reinstatement test. In experiment 1, six groups were used: vehicle+saline (Veh+Sal), 5 mg/kg cocaine alone (Veh+Coc) or with CBD 30 or 60 mg/kg (CBD30+Coc, CBD60+Coc) and CBD alone (CBD30+Sal, CBD60+Sal). In experiment 2, four groups were used: exploration (Veh+Expl), social defeat (Veh+SD) and social defeat with CBD (CBD30+SD and CBD60+SD). Furthermore, the relative gene expression of the dopamine transporter (DAT) in the ventral tegmental area was measured. Results: All mice acquired cocaine CPP and extinguished it after three or four weeks. Only the groups treated with cocaine priming (Veh+Coc) or exposed to social defeat (Veh+SD) showed reinstatement of CPP. Interestingly, CBD itself did not induce reinstatement and blocked the reinstating effects of cocaine priming and social defeat. Furthermore, cocaine priming increased DAT gene expression in the ventral tegmental area and CBD completely reversed this effect. Conclusion: These results suggest that CBD could reduce reinstatement to cocaine seeking after a period of abstinence.

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Effects of Glucagon-Like Peptide-1 Receptor Agonist Exendin-4 on the Reinstatement of Cocaine-Mediated Conditioned Place Preference in Mice

Frontiers in Behavioral Neuroscience ◽

10.3389/fnbeh.2021.769664 ◽

2022 ◽

Vol 15 ◽

Author(s):

Changliang Zhu ◽

Lei Wang ◽

Jiangwei Ding ◽

Hailiang Li ◽

Din Wan ◽

...

Keyword(s):

Conditioned Place Preference ◽

Receptor Agonist ◽

Place Preference ◽

Cocaine Addiction ◽

The Novel ◽

Conditioning Period ◽

Cocaine Seeking ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Reinstatement Test

A high percentage of relapse to compulsive cocaine-taking and cocaine-seeking behaviors following abstinence constitutes a major obstacle to the clinical treatment of cocaine addiction. Thus, there is a substantial need to develop effective pharmacotherapies for the prevention of cocaine relapse. The reinstatement paradigm is known as the most commonly used animal model to study relapse in abstinent human addicts. The primary aim of this study is to investigate the potential effects of systemic administration of glucagon-like peptide-1 receptor agonist (GLP-1RA) exendin-4 (Ex4) on the cocaine- and stress-triggered reinstatement of cocaine-induced conditioned place preference (CPP) in male C57BL/6J mice. The biased CPP paradigm was induced by alternating administration of saline and cocaine (20 mg/kg), followed by extinction training and then reinstatement by either a cocaine prime (10 mg/kg) or exposure to swimming on the reinstatement test day. To examine the effects of Ex4 on the reinstatement, Ex4 was systemically administered 1 h after the daily extinction session. Additionally, we also explored the associated molecular basis of the behavioral effects of Ex4. The expression of nuclear factor κβ (NF-κβ) in the nucleus accumbens (NAc) was detected using Western blotting. As a result, all animals that were treated with cocaine during the conditioning period successfully acquired CPP, and their CPP response was extinguished after 8 extinction sessions. Furthermore, the animals that were exposed to cocaine or swimming on the reinstatement day showed a significant reinstatement of CPP. Interestingly, systemic pretreatment with Ex4 was sufficient to attenuate cocaine- and stress-primed reinstatement of cocaine-induced CPP. Additionally, the expression of NF-κβ, which was upregulated by cocaine, was normalized by Ex4 in the cocaine-experienced mice. Altogether, our study reveals the novel effect of Ex4 on the reinstatement of cocaine-induced CPP and suggests that GLP-1R agonists appear to be highly promising drugs in the treatment of cocaine use disorder.

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