Involvement of dopamine receptors on locomotor stimulation and sensitization elicited by the interaction of ethanol and mazindol in mice

We have previously observed that the combination of ethanol (EtOH) and the anorectic drug mazindol (MZ) produces more marked effects on behavior than either substance alone. In the present study we examined whether the repeat ed administration of the drug combination could induce sensitization to its motor activating effects in mice and, if so, whether this response could b e affected by dopamine (DA) receptors antagonists. Male Swiss albino mice w ere treated daily for 7 days with combined EtOH+MZ (1.2 g/kg, 5.0 mg/kg IP) , EtOH (1.2 g/kg IP), MZ (5.0 mg/kg IP), or control solution coadministered with the D-1 dopamine antagonist SCH-23390 (0.025 or 0.05 mg/kg IP), the m ixed dopamine antagonist haloperidol (0.05 or 0.075 mg/kg IP), or vehicle. After the injections on days 1, 7, and 10, mice were assessed in activity c ages at different time intervals. Repeated administration of MZ resulted in an enhancement of its locomotor activating effects, behavioral sensitizati on. Further, the combined EtOH+MZ treatment also resulted in sensitization to its locomotor effects. Moreover, the development of MZ and EtOH+MZ sensi tization was attenuated by both SCH-23390 and haloperidol. These data demon strate that following repeated MZ or EtOH+MZ exposure mice show locomotor s ensitization through DA receptor stimulation. Also, these findings suggest that a major determinant of combined anorectic-alcohol misuse may be the in creased stimulating effects produced by such combination. (C) 1999 Elsevier Science Inc.