HIPPOCAMPUS NOREPINEPHRINE, CAUDATE DOPAMINE AND SEROTONIN, AND BEHAVIORAL-RESPONSES TO THE STEREOISOMERS OF AMPHETAMINE AND METHAMPHETAMINE

Microdialysis in behaving animals was used to concomitantly characteri ze the dopamine and 5-HT responses in the caudate and the norepinephri ne response in the hippocampus to the D- and L-isomers of amphetamine and methamphetamine. Doses of all four drugs which promoted similar st ereotypy responses produced a D-amphetamine-like response profile of d opamine and dopamine metabolites, suggesting that all these drugs inte ract with dopamine systems to facilitate the release of transmitter. H owever, in contrast to the similar behavioral profiles, the magnitude of the dopamine responses diverged significantly. In addition, all fou r drugs increased extracellular norepinephrine and 5-HT, but the relat ive responses differed markedly from dopamine and from each other. The contrasting structure-activity relationships for these drugs likely r eflect their differential potency at the various neuronal uptake trans porters in promoting either transmitter release, and/or uptake blockad e. In addition, the interaction of each drug at the vesicular transpor ters, as well as the availability of a cytoplasmic pool of transmitter likely also contribute to the neurotransmitter response. Because of t he particularly divergent transmitter response profiles exhibited by L -methamphetamine, its behavioral and neurotransmitter effects were cha racterized over a more extended range of doses. Although the duration of the increase in extracellular dopamine was clearly proportional to dose, the dose-dependent increases in the magnitude of the dopamine re sponse did not parallel the behavioral profiles. The results of these studies indicate that, while the dopamine, norepinephrine and 5-HT res ponses to these drugs probably contribute to the expression of stimula nt-induced behaviors, simple relationships between the neurotransmitte r responses and the behavioral profiles were not evident.