AMPHETAMINE-INDUCED TIME-DEPENDENT SENSITIZATION OF DOPAMINE NEUROTRANSMISSION IN THE DORSAL AND VENTRAL STRIATUM - A MICRODIALYSIS STUDY IN BEHAVING RATS

The purpose of this study was to compare the effects of amphetamine ex posure on subsequent amphetamine-induced changes in behavior and dopam ine (DA) release in the dorsal and ventral striatum, as a function of time following the discontinuation of repeated amphetamine treatment. Rats were pretreated with either saline or an escalating-dose amphetam ine regimen, and then received a 0.5 mg/kg amphetamine ''challenge'' a fter either 3, 7, or 28 days of withdrawal. Animals tested after 28 da ys of withdrawal were hypersensitive (sensitized) to the locomotor-act ivating effects of amphetamine, and relative to control animals showed a significant enhancement in amphetamine-stimulated DA release in bot h the dorsal and ventral striatum, as revealed by in vivo microdialysi s. Animals tested after only 3 or 7 days of withdrawal showed neither behavioral sensitization nor enhanced amphetamine-stimulated DA releas e. These results establish that time-dependent changes in behavioral s ensitization to amphetamine are associated with time-dependent changes in amphetamine-stimulated DA release, and support the hypothesis that persistent sensitization-related changes in striatal DA neurotransmis sion contribute to the expression of behavioral sensitization. (C) 199 5 Wiley-Liss, Inc.