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 repeated administration of the drug combination could induce sensitization to its motor activating effects in mice and, if so, whether this response could be affected by dopamine (DA) receptors antagonists. Male Swiss albino mice were 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 mixed 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 cages at different time intervals. Repeated administration of MZ resulted in an enhancement of its locomotor activating effects, behavioral sensitization. Further, the combined EtOH+MZ treatment also resulted in sensitization to its locomotor effects. Moreover, the development of MZ and EtOH+MZ sensitization was attenuated by both SCH-23390 and haloperidol. These data demonstrate that following repeated MZ or EtOH+MZ exposure mice show locomotor sensitization through DA receptor stimulation. Also, these findings suggest that a major determinant of combined anorectic-alcohol misuse may be the increased stimulating effects produced by such combination. (C) 1999 Elsevier Science Inc.