title: Effects of galanin on cocaine-mediated conditioned place preference and ERK signaling in mice.
abstract: 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.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06508, USA.
authors.forename: Roopashree
authors.initials: R
authors.lastname: Narasimhaiah
authors.forename: Helen M
authors.initials: HM
authors.lastname: Kamens
authors.forename: Marina R
authors.initials: MR
authors.lastname: Picciotto
mesh_terms: 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
chemical_list: C456547:7-((9-fluorenylmethoxycarbonyl)cyclohexylalanyllysyl)amino-4-methylcoumarin; D003374:Coumarins; D044088:Receptors, Galanin; D019004:Galanin; D048049:Extracellular Signal-Regulated MAP Kinases; D003042:Cocaine