title: 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.
authors: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
authors: Yvonne E
authors: YE
authors: Ogbonmwan
authors: Neuroscience Program, Biomedical and Health Sciences Institute, University of Georgia, Athens, GA, USA.
authors: Natale R
authors: NR
authors: Sciolino
authors: Neuroscience Program, Biomedical and Health Sciences Institute, University of Georgia, Athens, GA, USA.
authors: Jessica L
authors: JL
authors: Groves-Chapman
authors: Department of Physiology and Pharmacology, University of Georgia, Athens, GA, USA.
authors: Kimberly G
authors: KG
authors: Freeman
authors: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
authors: Jason P
authors: JP
authors: Schroeder
authors: Department of Physiology and Pharmacology, University of Georgia, Athens, GA, USA.
authors: Gaylen L
authors: GL
authors: Edwards
authors: Neuroscience Program, Biomedical and Health Sciences Institute, University of Georgia, Athens, GA, USA.|Department of Psychology, University of Georgia, Athens, GA, USA.
authors: Philip V
authors: PV
authors: Holmes
authors: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
authors: David
authors: D
authors: Weinshenker
mesh_terms: D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000503:physiopathology / Q000517:prevention & control; D003216:Conditioning, Operant; D003374:Coumarins / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D058999:Drug-Seeking Behavior / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005108:Extinction, Psychological / Q000187:drug effects; D005625:Frontal Lobe / Q000378:metabolism*; D019004:Galanin / Q000037:antagonists & inhibitors; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012008:Recurrence; D012054:Reinforcement, Psychology; D012646:Self Administration
chemical_list: C456547:7-((9-fluorenylmethoxycarbonyl)cyclohexylalanyllysyl)amino-4-methylcoumarin; D003374:Coumarins; D018765:Dopamine Uptake Inhibitors; D019004:Galanin; D003042:Cocaine; D004298:Dopamine
keywords: Cocaine; cortex; dopamine; galanin; galnon; reinstatement