Potentiation of phencyclidine-induced dopamine-dependent behaviors in rats after pretreatments with serotonin-depletors.
This study was designed to assess whether phencyclidine (PCP) produces dopamine (DA)-dependent behaviors such as licking, gnawing and biting (which are not observed in normal rats) in rats after pretreatments with a tryptophan hydroxylase inhibitor, p-chlorophenylalanine (PCPA) and specific serotonergic neuronal toxin, p-chloroamphetamine (PCA). Apomorphine (APO, 0.5 mg/kg) and methamphetamine (MAP, 2.5 mg/kg) mainly induced DA-dependent behaviors, including rearing and sniffing with occasional licking, in the vehicle-pretreated rats. APO (0.5 mg/kg)-induced DA-dependent behaviors significantly increased in the PCA- and PCPA-pretreated rats, in which serotonergic activity was greatly depressed but dopaminergic activity was normal. MAP (2.5 mg/kg)-induced DA-dependent behaviors were also significantly increased in the PCA-pretreated rats but not PCPA-pretreated rats. On the other hand, at doses of 2.5-7.5 mg/kg, PCP mainly caused stereotyped behaviors such as head-weaving, backpedalling, turning and DA-dependent behavior, such as sniffing, in the vehicle-pretreated rats. The PCP-induced stereotyped behaviors were attenuated by pretreatment with PCA and PCPA. In contrast, PCP-induced DA-dependent behavior, sniffing, was converted into more intense behaviors such as licking, gnawing and biting by pretreatment with PCA. These effects of PCP were also observed in rats pretreated with PCPA, although the degree was less than that by pretreatment with PCA. These results may indicate that serotonergic neuronal systems inhibitory regulate dopaminergic systems in PCP-induced behavioral responses.
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D004298:Dopamine / Q000494:pharmacology*; D004357:Drug Synergism; D010134:Fenclonine / Q000494:pharmacology; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism* / Q000502:physiology; D013239:Stereotyped Behavior / Q000187:drug effects; D010133:p-Chloroamphetamine / Q000494:pharmacology
D012701:Serotonin; D008694:Methamphetamine; D010133:p-Chloroamphetamine; D010622:Phencyclidine; D001058:Apomorphine; D010134:Fenclonine; D004298:Dopamine