CONICET | Buscador de Institutos y Recursos Humanos

LACK OF GABAB(1) RECEPTORS MODIFIES NICOTINE BEHAVIOURAL RESPONSES IN MICE. Varani A 1, Calvo M 1 and Balerio G1,2 1ININFA (CONICET) y 2Cát. de Farmacología (FFYB, UBA) Junín 956, 5°Piso. Bs As E-mail: gbalerio@ffyb.uba.ar Nicotine (NIC) is one of the active components of tobacco and some of acute behavioural effects induced by NIC can contribute to its abuse potential in humans. We have demonstrated that the GABAB receptor agonist baclofen increased the hypolocomotion and decreased the antinociceptive effects induced by NIC. The aim of the present study was to evaluate the possible role of GABAB(1) receptors in responses induced by acute NIC administration by using knockout mice lacking the GABAB(1) receptor and their wild-type littermates. The animals were injected with NIC (0.5, 1, 3 and 6 mg/kg, sc) or saline and locomotor activity was measured 5 min later for a period of 10 min. The antinociceptive responses were determined by tail-inmersion and hot-plate tests, 15 and 16 min after NIC or saline injection, respectively. Acute NIC administration decreased locomotor activity and induced antinociceptive responses in the tail-inmersion test at the dose of 3 and 6 mg/kg (p<0.001) and in the hot-plate test only at the dose of 6 mg/kg (p<0.001), in wild-type animals. In knockout GABAB(1) mice NIC also induced hipolocomotion at the dose of 6 mg/kg (p<0.001). The antinociceptive effects in the hot plate test were absent, while in the tail-inmersion test these responses were lower than in their wild-type mice. These results demonstrated that some acute effects elicited by nicotine can be modulated by the endogenous GABAergic system and support the existence of a physiological interaction between these two systems. Supported by UBACYT B021 and B016. Presentación: POSTER