Escalating Dose-Binge Exposure to Amphetamine and Methamphetamine: Behavioral and Neurochemical Characterization

Abstract

We have used an escalating dose-binge (ED-B) regimen in rats to simulate a pattern of drug intake typically displayed by high-dose stimulant abusers. ED-B treatment results in the progressive emergence of a unique behavioral profile that could not be produced by any acute or single daily injection stimulant dose tested. Corresponding to this emergent behavioral profile, in vivo microdialysis revealed that the caudate-putamen dopamine response is significantly diminished whereas the nucleus accumbens dopamine response is unchanged or slightly increased. To further assess the relevancy of this model in the context of available neurochemical markers associated with various patterns of stimulant abuse, we determined how a methamphetamine ED-B treatment affects striatal dopamine integrity. Our data revealed a pattern of change in striatal dopamine levels, as well as in measures of the dopamine transporter and vesicular monoamine transporter that paralleled the findings in postmortem brain tissue from methamphetamine abusers. During the 30 days after the last binge exposure, the reduced dopamine levels and the altered behavioral response to subsequent methamphetamine challenge significantly recovered, suggesting that the functional consequences of the ED-B treatment may not be permanent.