Attenuation by baclofen of nicotine rewarding properties and nicotine withdrawal manifestations

作者：Varani Andres P; Aso Ester; Machado Moutinho Lirane; Maldonado Rafael; Balerio Graciela N^*

来源：Psychopharmacology, 2014, 231(15): 3031-3040.

DOI：10.1007/s00213-014-3469-6

• Nicotine
• Baclofen
• GABA(B) receptors
• Reward
• Withdrawal
• Mice

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. %26lt;br%26gt;The aim of the present study was to evaluate the possible role of GABA(B) receptor in responses induced by repeated nicotine administration in Swiss Webster mice. %26lt;br%26gt;Nicotine hydrogen tartrate salt (0.5 mg/kg, s.c.) administration induced rewarding properties in the conditioning place preference test. The GABA(B) 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. %26lt;br%26gt;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 GABA(B) receptor activity. This study now reveals a novel possible application of baclofen to develop new therapeutic strategies to achieve smoking cessation.

• 出版日期2014-8