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 exposure on subsequent amphetamine-induced changes in behavior and dopamine (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 amphetamine regimen, and then received a 0.5 mg/kg amphetamine "challenge" after either 3, 7, or 28 days of withdrawal. Animals tested after 28 days of withdrawal were hypersensitive (sensitized) to the locomotor-activating effects of amphetamine, and relative to control animals showed a significant enhancement in amphetamine-stimulated DA release in both the dorsal and ventral striatum, as revealed by in vivo microdialysis. Animals tested after only 3 or 7 days of withdrawal showed neither behavioral sensitization nor enhanced amphetamine-stimulated DA release. These results establish that time-dependent changes in behavioral sensitization 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 neurotransmission contribute to the expression of behavioral sensitization.
Paulson
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PE
Department of Psychology, University of Michigan, Ann Arbor 48104-1687, USA.
Robinson
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TE
D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000502:physiology*; D004298:Dopamine / Q000502:physiology*; D004334:Drug Administration Schedule; D008297:Male; D017551:Microdialysis; D051381:Rats; D011919:Rats, Inbred Strains; D009435:Synaptic Transmission / Q000187:drug effects*; D013997:Time Factors
D000661:Amphetamine; D004298:Dopamine