Neuronal mechanisms of phencyclidine-induced place aversion and preference in the conditioned place preference task

Yukihiro Noda, Toshitaka Nabeshima

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Abstract

Place conditioning paradigms are widely used for determining the motivational properties of drugs. Phencyclidine (PCP) has been a common drug of abuse during the past two decades and has a rewarding effect in animals. However, PCP produces place aversion in the conditioned place preference (CPP) task in animals. Here, we report the possible neuronal mechanisms of PCP-induced place aversion and preference in the CPP task in rodents. In naive rats and mice, PCP dose-dependently produced place aversion and PCP had a significant effect at the doses of 4 and 8 mg/kg in rats and mice, respectively. The aversive effect of PCP (4 mg/kg) in rats was significantly attenuated by ritanserin (3 and 10 mg/kg), a serotonin (5-HT2) receptor antagonist whereas the lesion of serotonergic (5 HT(ergic)) neurons by 5,7- dihydroxytryptamine (100 μg i.c.v.) and α-methyl-p-tyrosine (AMPT; 100 mg/kg) a tyrosine hydroxylase inhibitor, did not affect the aversive effect of PCP. In rats pretreated with PCP (10 mg/kg/day) for 14 days tolerance was developed to PCP (4 mg/kg)-induced place aversion. In rats and mice pretreated with PCP (10 mg/kg/day) for 28 days, however, PCP dose- dependently produced place preference but not aversion. The preferred effect of PCP (8 mg/kg) in mice preteated with PCP (10 mg/kg/day for 28 days) was significantly attenuated by AMPT (100 mg/kg) and 6-hydroxydopamine (100 μg i,c.v), a dopaminergic (DAergic) neurotoxin, but not by DSP-4 (30 mg/kg), a noradrenergic neurotoxin and ritanserin. In mice pretreated with methamphetamine (1 mg/kg/day) for 14 days, PCP (8 mg/kg) produced place preference. These findings suggest that 5-HTergic and DAergic systems are involved in the PCP-induced place aversion and preference, respectively, and some changes in the neuronal systems including DAergic systems, induced by repeated PCP treatment play a critical role in the addiction of PCP.

Original languageEnglish
Pages (from-to)607-611
Number of pages5
JournalMethods and Findings in Experimental and Clinical Pharmacology
Volume20
Issue number7
DOIs
Publication statusPublished - 01-09-1998
Externally publishedYes

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Phencyclidine
Ritanserin
Neurotoxins
5,7-Dihydroxytryptamine
Serotonin 5-HT2 Receptor Antagonists
Methamphetamine
Oxidopamine
Tyrosine 3-Monooxygenase
Street Drugs
Tyrosine
Rodentia
Serotonin
Neurons
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

Cite this

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title = "Neuronal mechanisms of phencyclidine-induced place aversion and preference in the conditioned place preference task",
abstract = "Place conditioning paradigms are widely used for determining the motivational properties of drugs. Phencyclidine (PCP) has been a common drug of abuse during the past two decades and has a rewarding effect in animals. However, PCP produces place aversion in the conditioned place preference (CPP) task in animals. Here, we report the possible neuronal mechanisms of PCP-induced place aversion and preference in the CPP task in rodents. In naive rats and mice, PCP dose-dependently produced place aversion and PCP had a significant effect at the doses of 4 and 8 mg/kg in rats and mice, respectively. The aversive effect of PCP (4 mg/kg) in rats was significantly attenuated by ritanserin (3 and 10 mg/kg), a serotonin (5-HT2) receptor antagonist whereas the lesion of serotonergic (5 HT(ergic)) neurons by 5,7- dihydroxytryptamine (100 μg i.c.v.) and α-methyl-p-tyrosine (AMPT; 100 mg/kg) a tyrosine hydroxylase inhibitor, did not affect the aversive effect of PCP. In rats pretreated with PCP (10 mg/kg/day) for 14 days tolerance was developed to PCP (4 mg/kg)-induced place aversion. In rats and mice pretreated with PCP (10 mg/kg/day) for 28 days, however, PCP dose- dependently produced place preference but not aversion. The preferred effect of PCP (8 mg/kg) in mice preteated with PCP (10 mg/kg/day for 28 days) was significantly attenuated by AMPT (100 mg/kg) and 6-hydroxydopamine (100 μg i,c.v), a dopaminergic (DAergic) neurotoxin, but not by DSP-4 (30 mg/kg), a noradrenergic neurotoxin and ritanserin. In mice pretreated with methamphetamine (1 mg/kg/day) for 14 days, PCP (8 mg/kg) produced place preference. These findings suggest that 5-HTergic and DAergic systems are involved in the PCP-induced place aversion and preference, respectively, and some changes in the neuronal systems including DAergic systems, induced by repeated PCP treatment play a critical role in the addiction of PCP.",
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N2 - Place conditioning paradigms are widely used for determining the motivational properties of drugs. Phencyclidine (PCP) has been a common drug of abuse during the past two decades and has a rewarding effect in animals. However, PCP produces place aversion in the conditioned place preference (CPP) task in animals. Here, we report the possible neuronal mechanisms of PCP-induced place aversion and preference in the CPP task in rodents. In naive rats and mice, PCP dose-dependently produced place aversion and PCP had a significant effect at the doses of 4 and 8 mg/kg in rats and mice, respectively. The aversive effect of PCP (4 mg/kg) in rats was significantly attenuated by ritanserin (3 and 10 mg/kg), a serotonin (5-HT2) receptor antagonist whereas the lesion of serotonergic (5 HT(ergic)) neurons by 5,7- dihydroxytryptamine (100 μg i.c.v.) and α-methyl-p-tyrosine (AMPT; 100 mg/kg) a tyrosine hydroxylase inhibitor, did not affect the aversive effect of PCP. In rats pretreated with PCP (10 mg/kg/day) for 14 days tolerance was developed to PCP (4 mg/kg)-induced place aversion. In rats and mice pretreated with PCP (10 mg/kg/day) for 28 days, however, PCP dose- dependently produced place preference but not aversion. The preferred effect of PCP (8 mg/kg) in mice preteated with PCP (10 mg/kg/day for 28 days) was significantly attenuated by AMPT (100 mg/kg) and 6-hydroxydopamine (100 μg i,c.v), a dopaminergic (DAergic) neurotoxin, but not by DSP-4 (30 mg/kg), a noradrenergic neurotoxin and ritanserin. In mice pretreated with methamphetamine (1 mg/kg/day) for 14 days, PCP (8 mg/kg) produced place preference. These findings suggest that 5-HTergic and DAergic systems are involved in the PCP-induced place aversion and preference, respectively, and some changes in the neuronal systems including DAergic systems, induced by repeated PCP treatment play a critical role in the addiction of PCP.

AB - Place conditioning paradigms are widely used for determining the motivational properties of drugs. Phencyclidine (PCP) has been a common drug of abuse during the past two decades and has a rewarding effect in animals. However, PCP produces place aversion in the conditioned place preference (CPP) task in animals. Here, we report the possible neuronal mechanisms of PCP-induced place aversion and preference in the CPP task in rodents. In naive rats and mice, PCP dose-dependently produced place aversion and PCP had a significant effect at the doses of 4 and 8 mg/kg in rats and mice, respectively. The aversive effect of PCP (4 mg/kg) in rats was significantly attenuated by ritanserin (3 and 10 mg/kg), a serotonin (5-HT2) receptor antagonist whereas the lesion of serotonergic (5 HT(ergic)) neurons by 5,7- dihydroxytryptamine (100 μg i.c.v.) and α-methyl-p-tyrosine (AMPT; 100 mg/kg) a tyrosine hydroxylase inhibitor, did not affect the aversive effect of PCP. In rats pretreated with PCP (10 mg/kg/day) for 14 days tolerance was developed to PCP (4 mg/kg)-induced place aversion. In rats and mice pretreated with PCP (10 mg/kg/day) for 28 days, however, PCP dose- dependently produced place preference but not aversion. The preferred effect of PCP (8 mg/kg) in mice preteated with PCP (10 mg/kg/day for 28 days) was significantly attenuated by AMPT (100 mg/kg) and 6-hydroxydopamine (100 μg i,c.v), a dopaminergic (DAergic) neurotoxin, but not by DSP-4 (30 mg/kg), a noradrenergic neurotoxin and ritanserin. In mice pretreated with methamphetamine (1 mg/kg/day) for 14 days, PCP (8 mg/kg) produced place preference. These findings suggest that 5-HTergic and DAergic systems are involved in the PCP-induced place aversion and preference, respectively, and some changes in the neuronal systems including DAergic systems, induced by repeated PCP treatment play a critical role in the addiction of PCP.

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