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Acute phencyclidine induces aversion, but repeated phencyclidine induces preference in the place conditioning test in rats

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Abstract

Phencyclidine (PCP) is a drug that has been widely abused in the past two decades. PCP produces place aversion, but not preference, in the place conditioning test. The present study examined PCP-induced place conditioning behavior in rats treated with PCP repeatedly. In naive rats, PCP (2–8 mg/kg i.p.) dose dependently produced place aversion, but did not produce any effect in rats treated with PCP (10 mg/kg i.p.) for 14 days, indicating that tolerance developed to PCP-induced place aversion on repeated PCP treatment. In rats treated with PCP (10 mg/kg i.p.) for 28 days, PCP (2–8 mg/kg i.p.) dose dependently produced place preference. These findings suggest that some changes in neuronal function induced by the repeated PCP treatment may play an important role in the addiction to this drug.

Introduction

Place conditioning is a widely used test for determining the motivational properties of drugs (Schechter and Calcagnetti, 1993). Phencyclidine (1-(1-phenylcyclohexyl)piperidine; PCP) is a drug that has been widely abused during the past two decades (Petersen and Stillman, 1978). PCP has a rewarding effect in rats (Poling et al., 1981); however, it produces place aversion in the place conditioning task in rats (Barr et al., 1985; Iwamoto, 1986; Kitaichi et al., 1995a).

Several previous studies have already demonstrated that repeated PCP treatment produces behavioral sensitization and tolerance; some dopaminergic neuronal system-mediated behaviors (hyperlocomotion, rearing and sniffing) are potentiated, while some serotonergic (5-HTergic) neuronal system-mediated behaviors (head-twitch, head-weaving, backpedaling and turning) are reduced (Nabeshima et al., 1987a; Kitaichi et al., 1995b; Noda et al., 1996). In the present study, we examined whether PCP-induced place conditioning properties are altered in rats pretreated with PCP repeatedly.

Section snippets

Materials and methods

All procedures involving animals and their care conformed with the international guidelines that are in compliance with `Principles of Laboratory Animal Care' (NIH publication No. 85-23, revised 1985).

Results

As shown in Fig. 1, PCP (4 and 8 mg/kg i.p.) significantly produced place aversion in a dose-dependent manner in naive rats. In rats pretreated with PCP (10 mg/kg i.p.) for 14 days, however, PCP (2–8 mg/kg i.p.) produced neither place preference nor place aversion. On the other hand, PCP (4 and 8 mg/kg) significantly induced place preference in a dose-dependent manner in rats pretreated with PCP (10 mg/kg i.p.) for 28 days (P<0.015, F(3,32)=6.845).

Discussion

Several previous studies have demonstrated that repeated PCP treatment produces various behavioral and neurochemical changes (Nabeshima et al., 1987a; Kitaichi et al., 1995b; Noda et al., 1996) and that both behavioral sensitization and tolerance depend on different neuronal systems, as described in Section 1. In the present study, we investigated whether effects of PCP on place conditioning behaviors in rats could be altered by repeated PCP treatment, because PCP produces place aversion,

Acknowledgements

This study was supported by a Grant for Drug Abuse Research from the Ministry of Health and Welfare of Japan, and grants from the Ministry of Education, Science and Culture, Japan (No. 08457027) and from SERM-JSPS Joint Research Project.

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