title: Effect of olanzapine on scopolamine induced deficits in differential reinforcement of low rate 72s (DRL-72s) schedule in rats: involvement of the serotonergic receptors in restoring the deficits.
abstract: Scopolamine, a non-selective muscarinic receptor antagonist has widespread central nervous system effects. Muscarinic receptors located in the central nervous system play a vital role in the modulation of impulsivity. The objective of the current study was to evaluate the effect of scopolamine on impulsivity using differential-reinforcement-of-low-rate 72-s schedule (DRL-72s) and to demonstrate the involvement of serotonergic receptors in mediating the effect of olanzapine (atypical antipsychotic) on scopolamine induced impulsivity. Scopolamine impaired the performance of the rats trained under DRL-72s schedule. Olanzapine reversed the deficits induced by scopolamine. We evaluated the effect of donepezil (cholinesterase inhibitor), SB-742457 (5-HT6 and 5-HT2a antagonist), and haloperidol (typical antipsychotic) in rats challenged with scopolamine in the DRL-72s schedule to identify the receptor(s) involved in reversing the deficits. SB-742457 partially reversed the deficits, but donepezil and haloperidol did not show any effects on the deficits induced by scopolamine. Olanzapine and SB-742457 shifted the peak location (PkL) towards longer IRT duration, indicating a decrease in motor impulsivity. Modulation of scopolamine-induced impulsivity by olanzapine could be partly due to its antagonistic action at 5-HT2a and 5-HT6 receptors, respectively. Superior effects of olanzapine on impulsivity in schizophrenic patients may be mediated through the antagonism of 5-HT2a and 5-HT6 receptors.
authors.affiliation: Discovery Research, Suven Life Sciences Ltd., Hyderabad-500 055, Andhra Pradesh, India; Department of Pharmaceutical Sciences, Jawaharlal Nehru Technological University Hyderabad, Kukatpally, Hyderabad-500 085, Andhra Pradesh, India.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Jayarajan
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Nirogi
authors.forename: Anil
authors.initials: A
authors.lastname: Shinde
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D001569:Benzodiazepines / Q000494:pharmacology* / Q000627:therapeutic use; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D003216:Conditioning, Operant; D000077265:Donepezil; D006220:Haloperidol / Q000494:pharmacology; D007175:Impulsive Behavior / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D007189:Indans / Q000494:pharmacology; D008297:Male; D018727:Muscarinic Antagonists; D000077152:Olanzapine; D010880:Piperidines / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D012054:Reinforcement, Psychology; D012601:Scopolamine; D012702:Serotonin Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D013450:Sulfones / Q000494:pharmacology
chemical_list: C548140:3-benzenesulfonyl-8-piperazin-1-ylquinoline; D014150:Antipsychotic Agents; D002800:Cholinesterase Inhibitors; D007189:Indans; D018727:Muscarinic Antagonists; D010880:Piperidines; D011804:Quinolines; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013450:Sulfones; C097216:serotonin 6 receptor; D001569:Benzodiazepines; D000077265:Donepezil; D012601:Scopolamine; D006220:Haloperidol; D000077152:Olanzapine
keywords: DRL-72s; Donepezil; Haloperidol; Impulsivity; Olanzapine; SB-742457; Scopolamine