Development of tolerance and supersensitivity to phencyclidine in rats after repeated administration of phencyclidine

Toshitaka Nabeshima, Hiroaki Fukaya, Kazumasa Yamaguchi, Kazuhiro Ishikawa, Hiroshi Furukawa, Tsutomu Kameyama

Research output: Contribution to journalArticle

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Abstract

In rats treated with phenyclidine (PCP) repeatedly (PCP 10 mg/kg per day for 14 days), the back-pedalling, head-weaving and turning induced by PCP were attenuated (tolerance), while PCP-induced sniffing, rearing and ambulation were potentiated (supersensitivity). The behavior induced by the direct and indirect serotonin (5-HT) agonists, 5-methoxy-N,N-dimethyltryptamine and p-chloroamphetamine, was attenuated, while the sniffing, rearing or licking induced by the direct and indirect dopamine (DA) agonists, apomorphine and methamphetamine, were potentiated in the chronic PCP-treated rats. The DA and 5-HT contents in the nucleus accumbens and the ratio of HVA to DA in the striatum increased following the repeated PCP administration. Pentobarbital-induced sleep time did not change in the chronic PCP-treated rats as compared with the control rats. In addition, there was no significant difference between the disappearance rate of PCP in the brain of the rats treated with PCP repeatedly and the rate in the control rats. These results suggest that functional changes in the dopaminergic and serotonergic neuronal systems develop on repeated administration of PCP but that such changes do not develop in the hepatic drug-metabolizing system. In addition, tolerance develops in the serotonergic neuronal system while supersensitivity develops in the dopaminergic neuronal system. Biochemical findings suggest that increased mesolimbic dopaminergic neuronal function plays an important role in the development of the supersensitivity.

Original languageEnglish
Pages (from-to)23-33
Number of pages11
JournalEuropean Journal of Pharmacology
Volume135
Issue number1
DOIs
Publication statusPublished - 03-03-1987
Externally publishedYes

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Phencyclidine
Dopamine
Serotonin
Methoxydimethyltryptamines
p-Chloroamphetamine
Serotonin Receptor Agonists
Methamphetamine
Apomorphine
Dopamine Agonists
Nucleus Accumbens
Pentobarbital
Walking
Foot
Sleep
Head
Liver
Brain
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Nabeshima, Toshitaka ; Fukaya, Hiroaki ; Yamaguchi, Kazumasa ; Ishikawa, Kazuhiro ; Furukawa, Hiroshi ; Kameyama, Tsutomu. / Development of tolerance and supersensitivity to phencyclidine in rats after repeated administration of phencyclidine. In: European Journal of Pharmacology. 1987 ; Vol. 135, No. 1. pp. 23-33.
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Development of tolerance and supersensitivity to phencyclidine in rats after repeated administration of phencyclidine. / Nabeshima, Toshitaka; Fukaya, Hiroaki; Yamaguchi, Kazumasa; Ishikawa, Kazuhiro; Furukawa, Hiroshi; Kameyama, Tsutomu.

In: European Journal of Pharmacology, Vol. 135, No. 1, 03.03.1987, p. 23-33.

Research output: Contribution to journalArticle

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