Resumo

Rationale: Behavioral sensitization to the stimulant effects of ethanol (EtOH) or other drugs, observed in mice as increased locomotor activity (LA) after repeated drug administration, has been associated with neuroadaptations in the dopaminergic reward system (mesocorticolimbic pathways.In the nucleus accumbens (Nacc), dopamine release can be modulated by serotonergic 5HT2C receptors. Although i.p. administration of 5HT2C antagonists potentiates the stimulant effect of drugs, increasing LA, its direct administration in the Nacc reduces LA. However, no studies were developed on the effects of 5HT2C antagonists on the behavioral sensitization to ethanol. Objective: To evaluate if a systemic administration of a selective 5HT2C antagonist (SB242084) affects the expression of behavioral sensitization to EtOH. Method: Swiss albino male mice received 2.2 g/kg EtOH (N=52) or saline (N=26) daily for 21 days, having their locomotor activity (LA) weekly evaluated. All drugs were i.p. administered. According mice LA levels on the 21st day of treatment, EtOH-pretreated mice were classified into 3 subgroups: sensitized (higher levels), intermediate and non-sensitized (lower levels). Fourteen days after the 21st day of treatment mice were submitted to four pharmacological challenges, 48h apart from each other, being the first substance administered 30 min before the second: 1) Saline + saline; 2) saline + ETOH 2.2 g/kg; 3) SB242084 0.5 or 1.0 or 2.0 mg/kg + ETOH 2.2 g/kg; and 4) SB 242084 0.5 or 1.0 or 2.0 mg/Kg + saline. Mice LA was then immediately evaluated for 60 minutes. Results: The systemic administration of SB242084 did not affect sensitization expression (mean + S.E.M; for 0.5 mg/kg: saline= 1318.5 ± 429.8 ; non-sensitized= 1059.2 ± 247.1; sensitized= 2200.7 ± 571.5; for 1,0 mg/kg: saline = 1513.4 ± 691.8; non-sensitized= 1171.0 ± 314.3; sensitized= 2798.1 ± 677.3; for 2,0 mg/kg: saline= 838.4 ± 250.7; non-sensitized= 1348.2 ± 519.1 sensitized= 3092 ± 587.6). At none of the doses, did SB242084 affect LA per se (for 0.5 mg/kg: saline= 1860.6 ± 513.5; non-sensitized= 692 ± 346.6; sensitized= 1147 ± 496.2; for 1,0 mg/kg: saline = 1289.7 ± 515.5; non-sensitized= 562.2 ± 166 sensitized= 1490.5 ± 525.7; for 2,0 mg/kg: saline = 1247 ± 375.3; non-sensitized= 905.1 ± 370.8 sensitized= 1406.6 ± 527.9 ). Conclusion: Some studies reported that SB242084 potentiates the stimulation of LA induced by amphetamine, methamphetamine or nicotine. However, it did not affect LA of mice chronically treated with ethanol, even using higher doses of SB242084 than in other studies. These data suggest that 5HT2C receptors involvement in the expression of behavioral sensitization does not share the same mechanisms of interaction described in relation to the above mentioned stimulant drugs.