The effect of zotepine, risperidone, clozapine and olanzapine on MK-801-disrupted sensorimotor gating.
Dizocilpine (MK-801; 0.3 mg/kg i.p.)-induced disruption in prepulse inhibition of the acoustic startle response (PPI) can be preferentially restored by "atypical" antipsychotics. In contrast, some findings indicate that not all of the "atypical" antipsychotics, such as clozapine and risperidone, are effective in restoring the NMDA antagonist-induced deficits in PPI. In our study, we evaluated the effect of four different "atypical" antipsychotic drugs on deficits in PPI induced by MK-801. Zotepine and risperidone have high affinities to D2-like and 5-HT2A receptors, while clozapine and olanzapine have multipharmacological profiles with the highest affinities to serotonin 5-HT1A,2A/2C receptors and muscarinic receptors. Results have shown that MK-801 disrupted PPI and increased the ASR in rats. Our results showed no effect of zotepine (1 and 2 mg/kg) and risperidone (0.1 and 1 mg/kg) on disrupted PPI by MK-801. Administration of clozapine (5 and 10 mg/kg) and olanzapine (2.5 and 5 mg/kg) restored the deficits in PPI induced by MK-801. Additionally, we found a decrease of approximately 46% in PPI after administration of clozapine (5 mg/kg) and olanzapine (2.5 and 5 mg/kg) without MK-801 treatment. In summary, the four "atypical" antipsychotics had different efficacies to restore the disrupted PPI by MK-801. Only clozapine and olanzapin restored the MK-801-induced deficits in PPI.
Bubeníková
Vera
V
Prague Psychiatric Center affiliated with the Charles University 3rd Faculty of Medicine and the Center of Neuropsychiatric Studies, 181 03 Prague 8, Czech Republic. bubenikova@pcp.lf3.cuni.cz
Votava
Martin
M
Horácek
Jirí
J
Pálenícek
Tomás
T
Dockery
Colleen
C
D000161:Acoustic Stimulation; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology*; D003024:Clozapine / Q000494:pharmacology*; D003988:Dibenzothiepins / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D000077152:Olanzapine; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000819:agonists; D011976:Receptors, Muscarinic / Q000187:drug effects; D013216:Reflex, Startle / Q000187:drug effects*; D018967:Risperidone / Q000494:pharmacology*
D014150:Antipsychotic Agents; D003988:Dibenzothiepins; D018691:Excitatory Amino Acid Antagonists; D044402:Receptor, Serotonin, 5-HT2A; D017448:Receptors, Dopamine D2; D011976:Receptors, Muscarinic; D001569:Benzodiazepines; D016291:Dizocilpine Maleate; D003024:Clozapine; D018967:Risperidone; D000077152:Olanzapine; C022172:zotepine