D9-tetrahydrocannabinol decreases somatic expression of mecamylamine-precipitated nicotine withdrawal

BALERIO G.N., BERRENDERO F., MALDONADO R.

Prague, Czech Republic

Congreso; Sixth IBRO World Congress of Neuroscience; 2003

D9-tetrahydrocannabinol decreases somatic expression of mecamylamine-precipitated nicotine withdrawal. Balerio G. N., Berrendero F., Maldonado R. Laboratori de Neurofarmacologia, Department de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain. Behavioural and pharmacological effects of  D9-tetrahydrocannabinol (THC) and nicotine are well known. However, the possible interactions between these two drugs of abuse remain unclear in spite of the current association of cannabis and tobacco in humans. The aim of the present study was to analyse the consequences of THC administration on the manifestations of nicotine physical dependence in mice. Mecamylamine (1 mg/kg, sc) precipitated several somatic signs of nicotine withdrawal in nicotine chronically treated mice (25 mg/kg/day, sc). Acute THC pre-treatment (0.3, 1 and 3 mg/kg, i.p.) significantly decreased the incidence of some nicotine withdrawal signs, such as wet-dog-shakes, paw tremors, scratches and teeth chattering. The global withdrawal score was also significantly attenuated by acute THC administration. In a next step, we evaluated whether this THC effect was due to possible adaptative changes induced by nicotine on the endogenous cannabinoid system. For this purpose, we analysed CB1 cannabinoid receptor binding by using [3H]CP-55,940 autoradiography and the efficacy of CB1 receptor activation by using WIN 55,212-2-stimulated [35S]-GTPgS binding in different brain regions after chronic nicotine administration. The results showed that the stimulation of GTP-binding proteins by WIN 55,212-2 was modified in some specific brain structures, although not overall changes were observed on this cannabinoid receptor activity. Taken all together, these results indicate that THC administration attenuated nicotine withdrawal and that some specific adaptative changes produced by nicotine on the endogenous cannabinoid system could participate in this THC response.