Haloperidol-induced within-session response decrement patterns and catalepsy in rats: behavioural dissociation.
The typical antipsychotic haloperidol is known to induce extra-pyramidal side-effects (EPS). Catalepsy in rats is generally regarded as a valid model for detecting the EPS liability of compounds in humans. Together with its antipsychotic 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-course of haloperidol-induced catalepsy, measured by a bar test, to the haloperidol-induced within-session response decrements, measured by operant behaviour 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 either 30, 90 or 180 min prior to behavioural testing. The number of lever presses, food tray visits and latency to press the lever and to visit the food tray 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 forepaws on a horizontal bar. The latency to remove both forepaws from the bar 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 significantly after 180 min. Latency to visit the tray was affected only after 30 min, at 0.3 mg/kg. Haloperidol induced a dose-dependent increase in catalepsy 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 latter and both latency measures, was found. Consequently, the present data suggest that within-session response decrements are not obviously caused by catalepsy-related impairments.
Drinkenburg
W H
WH
MRC Neurochemical Pathology Unit, Newcastle General Hospital, Newcastle upon Tyne, UK. w.drinkenburg@organon.nhe.akzonobel.nl
Keith
A B
AB
Sahgal
A
A
Andrews
J S
JS
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D002375:Catalepsy / Q000139:chemically induced*; D003216:Conditioning, Operant / Q000187:drug effects*; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D012055:Reinforcement Schedule; D013997:Time Factors
D014150:Antipsychotic Agents; D006220:Haloperidol