A Single High Dose of Methamphetamine Reduces Monoamines and Impairs Egocentric and Allocentric Learning and Memory in Adult Male Rats

Methamphetamine (MA) alters dopamine markers and cognitive function in heavy users. In rodents, there are MA dosing regimens that induce concordant effects using repeated administration at spaced intervals. These regimens are effective but complicate experiments designed to disentangle the effects of the drug on different brain regions in relation to their cognitive effects because of treatment spacing. In an effort to simplify the model, we tested whether a single dose of MA could induce the same monoamine and cognitive effects as multiple, spaced dosing without affecting survival. Adult male Sprague-Dawley rats were treated with 40 mg/kg MA subcutaneously once and tested starting 2 weeks later. MA-treated rats showed deficits in egocentric navigation in Cincinnati water maze, in spatial navigation in the Morris water maze, and in choosing a consistent problem-solving strategy in the Star water maze when given the option to show a preference. MA-treated rats had persistent dopamine and serotonin reductions in the neostriatum and nucleus accumbens, and serotonin reductions in the hippocampus of the same magnitude as in repetitive treatment models. The data demonstrate that a single dose recapitulates the neurocognitive and monoamine effects of multiple-dose regimens, thereby simplifying the model of MA-induced neurotoxicity.