Effects of chronic treatments with SM-9018, a potential atypical neuroleptic, on behavioral dopaminergic and serotonergic sensitivities in rats.
1. Changes in behavioral dopaminergic and serotonergic sensitivities were studied in rats after withdrawal of the chronic treatments with SM-9018 (0.1 mg/kg/day), a potential atypical neuroleptic, and with haloperidol (0.3 mg/kg/day) using continuous infusion pumps. 2. Administration of SM-9018 inhibited the rat locomotor activities to an extent similar to that of haloperidol during the course of the 2 weeks treatment. 3. The incidence of the apomorphine-induced stereotyped behaviors (e.g., sniffing, chewing, licking and biting) was negligibly affected by SM-9018 treatment, but was markedly enhanced by haloperidol treatment. 4. The incidence of the 5-hydroxytryptophan-induced wet dog shakes and 8-hydroxy-2-(di-n-propyl-amino)tetralin-induced flat body posture was unaffected by either treatment with SM-9018 or haloperidol. 5. These findings suggest that SM-9018 is weaker than haloperidol in inducing the behavioral dopaminergic hypersensitivity after its chronic treatment and has a lower propensity to cause tardive dyskinesia.
Ohno
Y
Y
Discovery Research Laboratories II, Research Center, Sumitomo Pharmaceuticals Co., Ltd., Osaka, Japan.
Ishida
K
K
Ishibashi
T
T
Ikeda
K
K
Kato
T
T
Nakamura
M
M
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D004298:Dopamine / Q000502:physiology*; D006220:Haloperidol / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology*; D054833:Isoindoles; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011187:Posture / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000502:physiology*; D013239:Stereotyped Behavior / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology*
D014150:Antipsychotic Agents; D007211:Indoles; D054833:Isoindoles; D013844:Thiazoles; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D006916:5-Hydroxytryptophan; D006220:Haloperidol; D001058:Apomorphine; C065533:perospirone; D004298:Dopamine