Attenuation by baclofen of nicotine rewarding properties and nicotine withdrawal manifestations

RATIONALE: Nicotine is a major active ingredient in tobacco and plays a major role in tobacco addiction. In rodents, repeated nicotine administration produces behavioral responses related to its addictive properties, such as reinforcing effects and physical dependence. OBJECTIVES: The aim of the present study was to evaluate the possible role of GABAB receptor in responses induced by repeated nicotine administration in Swiss Webster mice. RESULTS: Nicotine hydrogen tartrate salt (0.5 mg/kg, s.c.) administration induced rewarding properties in the conditioning place preference test. The GABAB receptor agonist, baclofen (3 mg/kg, i.p.) abolished the rewarding properties induced by nicotine hydrogen tartrate salt (0.5 mg/kg, s.c.). In addition, naloxone-precipitated nicotine withdrawal induced somatic manifestations, anxiety-like effects in the elevated plus maze test and dysphoric manifestations in the conditioned place aversion paradigm. Baclofen (2 and 3 mg/kg, i.p.) prevented the somatic manifestations and the anxiety-like effects associated with naloxone-precipitated nicotine withdrawal but not the dysphoric manifestations. CONCLUSIONS: These results showed that nicotine rewarding properties and negative aspects of nicotine withdrawal, such as anxiety-like effects and somatic manifestations, can be modulated by the GABAB receptor activity. This study now reveals a novel possible application of baclofen to develop new therapeutic strategies to achieve smoking cessation.This work has been supported by grants from University of Buenos Aires (UBACyT B016 and UBACyT 2013-2016 Nº 20020120100244), CONICET (PIP 11420090100303), Spanish “Ministerio de Ciencia e Innovación” (#SAF2011-29864), “Instituto de Salud Carlos III” (RETICS: #RD06/0001/0001, #RD06/0001/1004), Plan Nacional sobre Drogas (PNSD#2009/026), the CatalanGovernment/n(SGR2009-00131), and the ICREA Foundation (ICREA Academia-2008). Andrés P. Varani is a doctoral fellow of the University of Buenos Aires (677/10)