Amphetamine sensitization augments amphetamine-induced Fos expression in the lateral habenula.

Repeated amphetamine (AMPH) administration results in behavioral sensitization. To investigate the neuroanatomical basis of this phenomenon, we examined the effects of AMPH sensitization on AMPH-induced Fos expression in 24 regions of the rat brain. Rats received repeated injections of AMPH (4 mg/kg, intraperitoneally, once every other day, eight times in total) or saline (same schedule as for AMPH). After a 14-day drug abstinence period, rats were challenged with 2 mg/kg AMPH intraperitoneally. As measured by Fos immunohistochemistry, the AMPH sensitization procedure enhanced subsequent AMPH-induced Fos expression in only one structure, the medial part of the lateral habenula. These results indicate that AMPH-induced behavioral sensitization is not accompanied by widespread increases in the ability of AMPH to increase regional Fos expression in the forebrain. The lateral habenula appears to be involved in the possible neural framework that is responsible for the expression of behavioral sensitization.