Effects of chlorpromazine and diazepam on time estimation behavior and motivation in rats.
The effects of chlorpromazine and diazepam on performance of two operant tasks, one modelling time estimation and the other motivation to work for food reinforcers, were investigated in rats. These same tasks had been used previously in rhesus monkeys to assess the effects of chlorpromazine and diazepam. Rat performance of the time estimation task [temporal response differentiation (TRD)] was nearly identical to that previously described in monkeys. This performance similarity across these two species occurred despite slightly different methodologies. Performance of the motivation task [progressive ratio (PR)] was clearly different between rats and adult monkeys in that rats exhibited lower values on all PR endpoints. Acute administration of chlorpromazine [0.03-5.6 mg/kg, intraperitoneally (IP)] caused decrements in rat TRD and PR performance at doses > or = 1.0 mg/kg. Acute administration of diazepam (0.25-4.0 mg/kg, IP) altered TRD performance only. The effects of chlorpromazine and diazepam in rats were similar to those previously noted in the monkey, indicating the potential utility of rat performance in these operant tasks to predict drug effects in the rhesus monkey.
Ferguson
S A
SA
Division of Neurotoxicology, National Center for Toxicological Research, Jefferson, AR 72079, USA. sferguson@fdant.nctr.fda.gov
Paule
M G
MG
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002746:Chlorpromazine / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018737:Hand Strength / Q000502:physiology; D008297:Male; D009042:Motivation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D013998:Time Perception / Q000187:drug effects*
D014151:Anti-Anxiety Agents; D014150:Antipsychotic Agents; D003975:Diazepam; D002746:Chlorpromazine