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The galanin receptor agonist, galnon, attenuates cocaine-induced reinstatement and dopamine overflow in the frontal cortex.

ABSTRACT: Relapse represents one of the most significant problems in the long-term treatment of drug addiction. Cocaine blocks plasma membrane monoamine transporters and increases dopamine (DA) overflow in the brain, and DA is critical for the motivational and primary reinforcing effects of the drug as well as cocaine-primed reinstatement of cocaine seeking in rats, a model of relapse. Thus, modulators of the DA system may be effective for the treatment of cocaine dependence. The endogenous neuropeptide galanin inhibits DA transmission, and both galanin and the synthetic galanin receptor agonist, galnon, interfere with some rewarding properties of cocaine. The purpose of this study was to further assess the effects of galnon on cocaine-induced behaviors and neurochemistry in rats. We found that galnon attenuated cocaine-induced motor activity, reinstatement and DA overflow in the frontal cortex at a dose that did not reduce baseline motor activity, stable self-administration of cocaine, baseline extracellular DA levels or cocaine-induced DA overflow in the nucleus accumbens (NAc). Similar to cocaine, galnon had no effect on stable food self-administration but reduced food-primed reinstatement. These results indicate that galnon can diminish cocaine-induced hyperactivity and relapse-like behavior, possibly in part by modulating DA transmission in the frontal cortex.

SUBMITTER: Ogbonmwan YE

PROVIDER: S-EPMC4305031 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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The galanin receptor agonist, galnon, attenuates cocaine-induced reinstatement and dopamine overflow in the frontal cortex.

Ogbonmwan Yvonne E YE Sciolino Natale R NR Groves-Chapman Jessica L JL Freeman Kimberly G KG Schroeder Jason P JP Edwards Gaylen L GL Holmes Philip V PV Weinshenker David D

Addiction biology 20140723 4

Relapse represents one of the most significant problems in the long-term treatment of drug addiction. Cocaine blocks plasma membrane monoamine transporters and increases dopamine (DA) overflow in the brain, and DA is critical for the motivational and primary reinforcing effects of the drug as well as cocaine-primed reinstatement of cocaine seeking in rats, a model of relapse. Thus, modulators of the DA system may be effective for the treatment of cocaine dependence. The endogenous neuropeptide g ...[more]

PMID: 25053279

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Project description: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.

Dataset Information

The galanin receptor agonist, galnon, attenuates cocaine-induced reinstatement and dopamine overflow in the frontal cortex.

Publications

The galanin receptor agonist, galnon, attenuates cocaine-induced reinstatement and dopamine overflow in the frontal cortex.

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