Escalating dose-binge stimulant exposure: relationship between emergent behavioral profile and differential caudate-putamen and nucleus accumbens dopamine responses.
Previous studies showed that treatment with high doses of amphetamine (8.0 mg/kg) administered according to an escalating dose-binge regimen, produced a unique behavioral profile that included a decrease in the duration of stereotypy and a pronounced increase in ambulation, characterized by a repeated bursting pattern of locomotion. This treatment regimen also resulted in differential dopamine response profiles in the caudate-putamen and nucleus accumbens: the dopamine response in the caudate-putamen exhibited a progressive within and between binge decline in peak levels, whereas the dopamine response in the nucleus accumbens was not significantly altered. The present study was designed to determine if this behavioral/dopamine response relationship was obtained under two additional conditions: first, in response to a relatively low dose amphetamine challenge (2.5 mg/kg) after withdrawal from escalating dose-binge treatment with either amphetamine or methamphetamine (6.0 mg/kg), and, second, during a lower dose (2.5 mg/kg amphetamine) escalating dose-binge regimen. Both the emergent behavioral profile and the regional differences in the dopamine response patterns were obtained under each set of conditions. These effects may be significantly implicated in the induction of stimulant psychosis, since the psychotogenic effects of amphetamine-like stimulants are most commonly associated with frequent, relatively high dose binge exposures.
Segal
D S
DS
Department of Psychiatry, School of Medicine, University of California, San Diego, La Jolla 92093, USA. dsegal@ucsd.edu
Kuczenski
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R
D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D015259:Dopamine Agents; D008694:Methamphetamine; D000661:Amphetamine; D004298:Dopamine