Baclofen attenuates the somatic expression, but not the motivational manifestations of nicotine withdrawal in mice

BALERIO G. N; ASO E.; MALDONADO R.

Geneva, Suiza

Congreso; 6th FENS Forum of European Neuroscience; 2008

Federation of European Neuroscience Societes/FENS

Baclofen attenuates the somatic expression, but not the motivational manifestations of nicotine withdrawal in mice. Balerio G 1, 2, Aso E 3 and Maldonado R 3 1Instituto de Investigaciones Farmacológicas (CONICET).  2Cát. de Farmacología, Fac. de Farmacia y Bioquímica (Universidad de Buenos Aires).  Junín 956, 5º Piso (C1113AAD) Buenos Aires-Argentina. 3Laboratorio de Neurofarmacología, Universitat Pompeu Fabra, Barcelona, España. E-mail: gbalerio@ffyb.uba.ar. Nicotine (NIC) is one of the active components of tobacco and play a major role in tobacco addiction. Previous studies in rodents have shown that NIC modifies locomotion, anxiety, nociception, learning and memory. Repeated nicotine administration in animals produces several behavioural responses closely related to its addictive properties, such as reinforcing effects and physical dependence.  The aim of the present study was to evaluate the possible role of GABAB receptor in the responses induced by acute and repeated NIC administration in CD1 mice. Acute NIC (3 mg/kg, sc) administration decreased locomotor activity and induced antinociceptive responses in the tail-immersion and the hot-plate test. The GABAB receptor agonist baclofen (BAC) (2 mg/kg, i.p.) increased the hypolocomotion induced by NIC and decreased the antinociceptive effects in the hot-plate test. In addition, a model of naloxone-induced abstinence in chronic NIC-treated mice (25 mg/kg/day, sc) was developed. Naloxone (3 mg/kg, sc) precipitated several somatic signs of NIC withdrawal in dependent mice and BAC attenuated the severity of those somatic signs of NIC withdrawal. However, BAC administration did not modify the aversive motivational state associated to naloxone precipitated NIC withdrawal evaluated by the place aversion conditioning paradigm. These results demonstrated that the somatic expression, but not the aversive motivational consequences of NIC withdrawal can be modulated by the endogenous GABAergic system. Supported by UBACYT B021, Subsidio Florencio Fiorini and Ministerio de Ciencia y Tecnología de España