Haloperidol-induced supersensitivity to the discrimination of apomorphine

Rats were trained to discriminate between the stimulus properties of intraperitoneal 0.16 mg/kg apomorphine and saline in a two-lever, food-motivated operant task. Once trained, the rats were tested with the ED50 of apomorphine (0.02 mg/kg) or saline before and 1-22 days after a ten-day regimen of daily 2.0 mg/kg administrations of haloperidol. Chronic haloperidol treatment produced increased discrimination of, and lever selection perseverance to, the low dose of apomorphine when rats were tested at 12 days after the withdrawal of haloperidol and this increased discrimination returned to pre-haloperidol levels by the sixteenth day. The results suggest the development of supersensitivity by prolonged pharmacologic blockade of central dopaminergic receptors with haloperidol and indicate the peak and duration of this effect.