Effects of methamphetamine and ethanol on learning and brain neurotransmitters in rats.

The interactions of methamphetamine (MAMP) and ethanol (EtOH) on multiple active/passive avoidance performance and neurotransmitters in different brain regions were examined. After the acquisition schedules, rats were retrained under the influence of MAMP (2 mg/kg/day, IP), EtOH (2 g/kg/day, IP), and in combination over 20 days in rats (n = 6 per group). As a function of progress of drug treatment, MAMP-EtOH mixtures disrupt the learned avoidance performance and produced severe impairment of discriminative behavior caused by enhancement of excitability induced by MAMP when compared with MAMP only. At withdrawal, MAMP-EtOH-induced impairments of performance significantly persisted, whereas MAMP-only-induced impairments slightly recovered. At the eleventh day drug withdrawal, MAMP-only-induced alterations of neurotransmitter levels at different regions were alleviated by EtOH, but these did not return to normal levels. These data provide support for the direct antagonistic and indirect additive interactions following constant daily treatment with a combination of MAMP and EtOH. EtOH may be an important factor in MAMP abuse to MAMP-induced psychosis or neurotoxicity.