Rapid recovery of self-stimulation from depression produced by the atypical neuroleptic risperidone is not prevented by 5-HT2 receptor stimulation.
Behavioral effects of the antipsychotic drug risperidone were tested in rats responding for variable-interval stimulation of the ventral tegmental area (VTA). Risperidone (0-0.9 mg/kg) produced a dose-dependent depression of responding in the 60 min after injection. Self-stimulation tests delayed for 30 or 120 min after injection showed that inhibition of responding by risperidone was limited in duration, with response rates recovering to pre-injection levels in a time-dependent manner. Recovery occurred regardless of opportunity to engage in self-stimulation, and was virtually complete at a time when receptor occupancy has been shown to be almost undiminished. The atypical properties of risperidone have been ascribed to its potent antagonist activity at 5-HT2 receptors; however, spontaneous recovery from the effects of risperidone was not prevented by simultaneous administration of a selective 5-HT2 agonist (DOI), even though DOI when given alone produced a 50-70% reduction in response rates. These results show that the inhibitory effect of risperidone on operant performance may be self-limiting in a manner that is not accounted for by its pharmacokinetic properties nor by its antagonist activity at central 5-HT2 receptors.
Grottick
A J
AJ
Institute of Neurology, National Hospital, London, UK.
Montgomery
A M
AM
Herberg
L J
LJ
D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects; D018967:Risperidone / Q000494:pharmacology*; D012653:Self Stimulation / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D000662:Amphetamines; D014150:Antipsychotic Agents; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D018967:Risperidone; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine