title: Mice lacking the galanin gene show decreased sensitivity to nicotine conditioned place preference.
abstract: Previous work has indicated that the neuropeptide galanin decreases sensitivity to the rewarding effects of morphine and cocaine, but increases alcohol drinking. The aim of the current study was to examine the role of galanin signaling in nicotine reward by testing the effects of nicotine in mice lacking galanin peptide (GAL-/-) as compared to wild-type (GAL+/+) controls. Using an unbiased, three-chamber conditioned place preference (CPP) paradigm the dose-response function for nicotine CPP was tested in GAL-/- and GAL+/+ mice. Since activation of extracellular signal-related kinase (ERK2) is involved in the rewarding effects of several classes of drugs of abuse, we then measured the level of ERK2 phosphorylation in the nucleus accumbens shell (NACsh) and core (NACco) of GAL-/- and GAL+/+ mice following re-exposure to the CPP chamber previously paired with nicotine as a marker of mesolimbic system activation. Finally, we examined whether acute nicotine administration affects ERK2 activity in GAL-/- and GAL+/+ mice. GAL-/- mice required a higher dose of nicotine to induce a significant CPP compared to GAL+/+ mice. In the conditioning groups showing significant expression of nicotine CPP, only GAL+/+ mice showed ERK2 activation in the NACsh. This suggests that the nicotine CPP observed in GAL+/+ mice resulted in differential recruitment of ERK signaling in the NACsh compared to GAL-/- mice. In addition, no activation of ERK2 was observed following acute nicotine administration in either genotype. These data, along with prior results, suggest that galanin alters sensitivity to drugs of abuse differentially, with morphine, cocaine and amphetamine place preference suppressed, and nicotine and alcohol preference increased, by galanin signaling.
authors.affiliation: Division of Molecular Psychiatry, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University School of Medicine, New Haven, CT 06508, United States.
authors.forename: Nichole M
authors.initials: NM
authors.lastname: Neugebauer
authors.forename: Robert M
authors.initials: RM
authors.lastname: Henehan
authors.forename: Claire A
authors.initials: CA
authors.lastname: Hales
authors.forename: Marina R
authors.initials: MR
authors.lastname: Picciotto
mesh_terms: D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology*; D019004:Galanin / Q000172:deficiency* / Q000235:genetics; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D020297:Mice, Congenic; D018345:Mice, Knockout; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D009020:Morphine / Q000494:pharmacology; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology; D010766:Phosphorylation; D012201:Reward; D015398:Signal Transduction; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D009538:Nicotine; D009020:Morphine; D019004:Galanin; D019950:Mitogen-Activated Protein Kinase 1; D003042:Cocaine