Haloperidol-induced within-session response decrement patterns and catalepsy in rats: behavioural dissociation

The typical antipsychotic haloperidol is known to induce extra-pyramidal si de-effects (EPS). Catalepsy in rats is generally regarded as a valid model for detecting the EPS liability of compounds in humans. Together with its a ntipsychotic and cataleptogenic actions, haloperidol causes an attenuation of instrumental responding which becomes larger in the course of a session: a within-session response decrement. The present study compared the time-c ourse of haloperidol-induced catalepsy, measured by a bar test, to the halo peridol-induced within-session response decrements, measured by operant beh aviour under a fixed ratio 10 schedule of reinforcement. Rats were trained to press a lever on a Fixed Ratio 10 schedule of food reinforcement during sessions of 15 min. When responding was stable, saline or haloperidol in 0. 03 mg/kg, 0.1 mg/kg, or 0.3 mg/kg was administered intra-peritoneally eithe r 30, 90 or 180 min prior to behavioural testing. The number of lever press es, food tray visits and latency to press the lever and to visit the food t ray were analysed in five successive blocks of 3 min. Catalepsy was tested 30, 60, 90, 120, and 180 min. after injection, by placing a rat with its fo repaws on a horizontal bar. The latency to remove both forepaws from the ba r was scored. Within-session response decrements were present at 0.1 mg/kg and at 0.3 mg/kg, from 30 min after administration onward. At these doses, latency to press the lever was increased after 30 and 90 min, but not signi ficantly after 180 min. Latency to visit the tray was affected only after 3 0 min, at 0.3 mg/kg. Haloperidol induced a dose-dependent increase in catal epsy from 60 min onwards, with maximal effect after 120 min. A dissociation between the time-course of occurrence of within-session response decrement and the cataleptogenic action of haloperidol, as well as between the latte r and both latency measures,,vas found. Consequently, the present data sugg est that within-session response decrements are not obviously caused by cat alepsy-related. impairments, (C) 1999 Lippincott Williams & Wilkins.