Partial agonistic effects of OPC-14597, a potential antipsychotic agent, on yawning behavior in rats.
The present experiments were performed to examine the behavioral effects of OPC-14597, which acts on dopamine receptors in rats. OPC-14597 administered subcutaneously (SC) at doses of 0.1-5 mg/kg elicited yawning, as did OPC-4392 (0.5-2 mg/kg, SC) and (-)-3-PPP (2.5-10 mg/kg, SC). These yawning responses were blocked by intraperitoneal (IP) pretreatment with haloperidol (0.5 mg/kg) but were increased by pindolol (20 mg/kg, IP) or reserpine (5 mg/kg, IP), which per se did not elicit yawning. The yawning induced by talipexole, a selective dopamine D2 receptor agonist, was inhibited by OPC-14597 (0.5-5 mg/kg, SC) and (-)-3-PPP (10 mg/kg, SC). Apomorphine (0.5 mg/kg, SC), a dopamine D1/D2 receptor agonist, elicited stereotypy such as sniffing and licking but OPC-14597 (5-20 mg/kg, SC) did not induce this behavior. The stereotypy induced by apomorphine was inhibited not only by haloperidol (0.5 mg/kg, IP) and (-)-3-PPP (10 mg/kg, SC) but also by OPC-14597 (5-20 mg/kg, SC), without being affected by OPC-4392 (2 mg/kg, SC). In 6-hydroxydopamine (6-OHDA)-treated rats, apomorphine (0.5 mg/kg, SC) elicited rotation behavior whereas OPC-14597, OPC-4392 and (-)-3-PPP did not produce this behavior. These findings suggest that OPC-14597 provokes yawning without causing stereotypy and rotation but markedly antagonizes the talipexole-induced yawning and apomorphine-induced stereotypy, and that OPC-14597 thus exerts partial agonistic effects on yawning behavior but antagonistic effects on stereotypy in rats.
Fujikawa
M
M
Department of Pharmacology, School of Medicine, Fukuoka University, Japan.
Nagashima
M
M
Inoue
T
T
Yamada
K
K
Furukawa
T
T
D000818:Animals; D014150:Antipsychotic Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000068180:Aripiprazole; D001381:Azepines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D004357:Drug Synergism; D008297:Male; D016627:Oxidopamine; D010879:Piperazines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010880:Piperidines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015363:Quinolones / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000187:drug effects; D013239:Stereotyped Behavior / Q000187:drug effects; D013563:Sympathectomy, Chemical; D015000:Yawning / Q000187:drug effects*
D014150:Antipsychotic Agents; D001381:Azepines; D018491:Dopamine Agonists; D010879:Piperazines; D010880:Piperidines; D015363:Quinolones; D011954:Receptors, Dopamine; C054574:OPC 4392; C024763:talipexole; D000068180:Aripiprazole; D016627:Oxidopamine; C026539:preclamol