Effects of galanin on cocaine-mediated conditioned place preference and ERK signaling in mice.
BACKGROUND
The neuropeptide galanin and its receptors are expressed in brain regions implicated in the rewarding effects of natural stimuli and drugs of abuse. Galanin has been shown to attenuate neurochemical, physiological, and behavioral signs of opiate and amphetamine reinforcement.


OBJECTIVE
In the current study, we present evidence that galanin modulates neurochemical and behavioral correlates of cocaine response.


METHODS
Mice lacking the neuropeptide galanin (Gal -/-) and wild-type (Gal +/+) controls were used to analyze the effects of galanin in an unbiased conditioned place preference paradigm. We then examined cocaine-induced activation of extracellular signal-regulated kinase (ERK) activity as a marker of intracellular signaling in the mesolimbic dopaminergic pathway induced by acute cocaine administration


RESULTS
Gal -/- mice showed significantly greater conditioned place preference at a threshold dose of cocaine (3 mg/kg) than Gal +/+ mice, and this was reversed by administration of the galanin receptor agonist galnon. Consistent with the results of behavioral experiments, there was a significant increase in ERK activation in the ventral tegmental area (VTA) and nucleus accumbens (NAc) of Gal -/- mice but not Gal +/+ mice following acute, systemic cocaine injection at the threshold dose. In the NAc, but not VTA, this effect was reversed by administration of galnon.


CONCLUSIONS
These data, coupled with previous studies on the effects of morphine and amphetamine, demonstrate that galanin normally attenuates drug reinforcement, potentially via modulation of the mesolimbic dopamine system.
Narasimhaiah
Roopashree
R
Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06508, USA.
Kamens
Helen M
HM
Picciotto
Marina R
MR
D000818:Animals; D015153:Blotting, Western; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000378:metabolism / Q000523:psychology*; D003216:Conditioning, Operant / Q000187:drug effects*; D003374:Coumarins / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D019004:Galanin / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009714:Nucleus Accumbens / Q000378:metabolism; D044088:Receptors, Galanin / Q000819:agonists; D012054:Reinforcement, Psychology; D017557:Ventral Tegmental Area / Q000378:metabolism
C456547:7-((9-fluorenylmethoxycarbonyl)cyclohexylalanyllysyl)amino-4-methylcoumarin; D003374:Coumarins; D044088:Receptors, Galanin; D019004:Galanin; D048049:Extracellular Signal-Regulated MAP Kinases; D003042:Cocaine