Reward system depression following chronic amphetamine: antagonism by haloperidol.

The effect of pre-treatment with haloperidol, a dopamine antagonist, on chronic amphetamine's suppression of intra-cranial self-stimulation of the lateral hypothalamus was investigated. Rats treated with 15 mg/kg d-amphetamine per day for seven days displayed a marked increase in reward threshold for electrical brain stimulation responding with an accompanying suppression of response rate. This disruption of intracranial self-stimulation responding was not observed when 30 min prior to each amphetamine injection, animals were injected with 1.0 mg/kg of haloperidol. This study demonstrates that post-synaptic mechanisms play an integral role in the development of chronic amphetamine depression, and suggests that changes at the dopamine receptor are involved in this reward system alteration.