RATIONALE: 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.
RATIONALE: 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: L F Kolakowski; G P O'Neill; A D Howard; S R Broussard; K A Sullivan; S D Feighner; M Sawzdargo; T Nguyen; S Kargman; L L Shiao; D L Hreniuk; C P Tan; J Evans; M Abramovitz; A Chateauneuf; N Coulombe; G Ng; M P Johnson; A Tharian; H Khoshbouei; S R George; R G Smith; B F O'Dowd Journal: J Neurochem Date: 1998-12 Impact factor: 5.372
Authors: Nichole M Neugebauer; Robert M Henehan; Claire A Hales; Marina R Picciotto Journal: Pharmacol Biochem Behav Date: 2010-12-21 Impact factor: 3.533
Authors: Joanna I Giza; Yonwoo Jung; Rachel A Jeffrey; Nichole M Neugebauer; Marina R Picciotto; Thomas Biederer Journal: Neuropsychopharmacology Date: 2012-11-21 Impact factor: 7.853
Authors: Emily B Einstein; Yukiko Asaka; Mark F Yeckel; Michael J Higley; Marina R Picciotto Journal: Eur J Neurosci Date: 2013-02-07 Impact factor: 3.386
Authors: Marina R Picciotto; Christian Brabant; Emily B Einstein; Helen M Kamens; Nichole M Neugebauer Journal: Brain Res Date: 2009-08-20 Impact factor: 3.252
Authors: Yvonne E Ogbonmwan; Natale R Sciolino; Jessica L Groves-Chapman; Kimberly G Freeman; Jason P Schroeder; Gaylen L Edwards; Philip V Holmes; David Weinshenker Journal: Addict Biol Date: 2014-07-23 Impact factor: 4.280