Acute behavioural responses to nicotine and nicotine withdrawal syndrome are modified in GABAB1 knouckout mice

VARANI A; LIRANE MACHADO MOUTINHO; BALERIO G

NEUROPHARMACOLOGY

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2012 vol. 63 p. 863 - 872

0028-3908

Nicotine acute behavioural responses and nicotine withdrawal syndrome are modified in GABAB1 knockout mice Varani A.P.a, Moutinho Machado L.a, Bettler B.b and Balerio G.N.a,c aININFA (UBA-CONICET), bPharmazentrum (UNIBASEL), cCát. de Farmacología (FFyB-UBA). Junín 956 5° Piso, Buenos Aires C1113AAD, Argentina. avarani@ffyb.uba.ar Nicotine is the main active component of tobacco and some of its acute and chronic pharmacological effects can contribute to its abuse potential in humans. The aim of the present study was to evaluate the possible role of GABAB receptors in several responses induced by acute and chronic nicotine administration by using GABAB1 knockout mice and their wild-type littermates. Acute nicotine (0.5, 1, 3 and 6 mg/kg, sc) administration decreased locomotor activity and induced antinociceptive responses in the tail-immersion and hot-plate tests, in wild-type mice. A hypolocomotive effect was observed only at the highest dose of nicotine, and the antinociceptive responses in both tests were significantly abolished in GABAB1 knockout mice. In addition, in wild-type mice nicotine (0.05 and 0.8 mg/kg, sc) elicited anxiolytic- and anxiogenic-like responses, respectively, in the elevated plus maze test. In GABAB1 knockout mice, the anxiolytic- but not the anxiogenic-like effect was abolished. A model of mecamylamine-induced abstinence in chronic nicotine-treated mice (25 mg/kg/day, sc) was developed. Mecamylamine (1 mg/kg, sc) precipitated several somatic signs of nicotine withdrawal in wild-type dependent mice. However, nicotine withdrawal was abolished in GABAB1 knockout mice. Finally, the Fos-like immunoreactivity analysis revealed a decrease of Fos-positive nuclei in the bed nucleus of the stria terminalis, basolateral amygdaloid nucleus and dentate gyrus of the hippocampus in abstinent wild-type mice, but not in GABAB1 knockout mice. These results suggest that some acute effects and dependence induced by nicotine could be modulated by the GABAergic system and support the existence of a possible interaction between these two systems.