Differential regional zif268 messenger RNA expression in an escalating dose/binge model of amphetamine-induced psychosis

Amphetamine-induced psychosis is most often associated with a high-dose mul tiple binge pattern of stimulant abuse. To simulate these conditions in rat s, we used an escalating dose/binge administration paradigm. Animals were p retreated with escalating doses of amphetamine (1.0-8.0 mg/kg) over four da ys, then exposed to nine daily binges (8.0 mg/kg every 2 h; four injections /day). Other animals received either multiple injections of saline, saline followed by acute amphetamine (8.0 mg/kg) or single daily injections of amp hetamine (8.0 mg/kg) in parallel with the escalating dose/binge treatment. One hour after the last injection, all animals were decapitated and regiona l brain activation patterns were assessed using in situ hybridization with antisense probes for zif268. Acute amphetamine resulted in a significant el evation of zif268 messenger RNA in both the nucleus accumbens and dorsal st riatum. However, whereas after single daily amphetamine treatment this inde x was no longer elevated above control levels in the dorsal striatum, multi ple binge exposures were required for the nucleus accumbens to return to ba seline. Agranular insular cortex and medial olfactory tubercle zif268 messe nger RNA expression was also markedly increased after acute amphetamine tre atment but, unlike the nucleus accumbens and dorsal striatum, this increase was not significantly attenuated by either single daily injection or multi ple binge treatment. Zif268 messenger RNA expression in the lateral nucleus of the amygdala also remained elevated above baseline after binge treatmen t. The possible relationships of these changes in zif268 messenger RNA regiona l expression patterns to the development of psychosis in high-dose stimulan t abusers are discussed. (C) 2000 IBRO. Published by Elsevier Science Ltd.