Differential effects of the new antipsychotic risperidone on large and small motor movements in rats: a comparison with haloperidol.
Risperidone, a new antipsychotic agent, was studied for its effects on spontaneous motor activity in rats in comparison with haloperidol. Motor activity was recorded via the optical scanning technique (horizontal and vertical activity) and via a recently developed technique based on the piezo-electric principle which, in contrast to optical scanning, is very sensitive to small, stationary movements (piezo activity). Risperidone and haloperidol at low doses depressed both vertical activity (ED50s: 0.062 and 0.038 mg/kg, respectively) and horizontal activity (0.18 and 0.060 mg/kg, respectively). With increase of dose, motor activity decline was significantly faster with haloperidol than with risperidone. Moreover, haloperidol also rapidly depressed piezo activity (ED50: 0.085 mg/kg) whereas risperidone depressed this component of motor behaviour at much higher doses only (ED50: 2.80 mg/kg). Visual inspection did not reveal abnormal behavioural movements following the test compounds. Risperidone, therefore, preserves normal small movements over a much larger dose interval than haloperidol; this effect may be related to its relatively low cataleptogenic activity and potentially also to a reduced EPS liability. The present results further confirm that the piezo technique may complement the optical scanning method, and thereby enhance the information on the extent that test compounds modify behaviour.
Megens
A A
AA
Department of Pharmacology, Janssen Research Foundation, Beerse, Belgium.
Awouters
F H
FH
Niemegeers
C J
CJ
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000494:pharmacology*; D007555:Isoxazoles / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010080:Oxazoles / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D018967:Risperidone
D014150:Antipsychotic Agents; D007555:Isoxazoles; D010080:Oxazoles; D010880:Piperidines; D006220:Haloperidol; D018967:Risperidone