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

doi:10.1016/0014-2999(87)90753-9

Cited by 69 publications

(50 citation statements)

References 35 publications

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“…This head-twitch is enhanced 2 weeks after the injection of the 5-HT-neurotoxin, 5,7-dihydroxytryptamine with the in crement of 5-HT2A-receptors (8). Furthermore, in rats that have received repeated administrations of PCP, toler ance is developed in the serotonergic neuronal system: the [3H]-spiperone binding capacity is reduced (34), and the frequency of PCP-induced head-twitch is decreased (15). These results suggest that PCP induces head-twitch via postsynaptic 5-HT2A-receptors.…”

Section: Discussionmentioning

confidence: 56%

“…1 hr after pretreatment with vehicle or drugs; and then the hyperlocomotion and stereotyped behaviors, i.e., rearing, sniffing, head-weaving, head-twitch, backpedalling and turning were measured for 90 min as described by Nabeshima et al (8,15). Briefly, hyperlocomotion was measured automatically over a 90-min period by using electric digital counters with infrared cell sensors placed on the walls (SCANET SV-10; Toyo Sangyou, Toyama).…”

Section: Measurementmentioning

confidence: 99%

“…In previous experiments, we reported that the hyperlocomotion and some of stereo typed behaviors induced by PCP were mediated by dopa minergic and serotonergic neuronal systems and that PCP-induced head-twitch via 5-HT2A receptors in rats (13)(14)(15)(16). Therefore, several investigators including us hypothesized that the drugs that block both PCP-induced dopamine and 5-HT-mediated stereotyped behaviors may possibly prevent both the positive and negative symp toms of schizophrenia (7 9).…”

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confidence: 99%

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Effects of Risperidone on Phencyclidine-Induced Behaviors: Comparison with Haloperidol and Ritanserin

Kitaichi

Yamada

Hasegawa

et al. 1994

Japanese Journal of Pharmacology

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ABSTRACT-In this study, we investigated whether risperidone, a serotonin-S2A (5-HT21)/dopamine-D2 (D2)-receptor antagonist, inhibits phencyclidine (PCP)-induced stereotyped behaviors in comparison with haloperidol and ritanserin. Moreover, we also attempted to investigate the effects of these antipsychotics on the contents of dopamine, serotonin (5-HT) and their metabolites in rat striatum and frontal cortex. In rats, PCP (5 mg/kg, i.p.) caused hyperlocomotion and stereotyped behaviors, including sniffing, head-weaving, backpedalling and turning. Both risperidone (0.8-2.4 mg/kg, p.o.) and haloperidol (0.3-1.0 mg/kg, p.o.) inhibited these behaviors, except for backpedalling, in a dose-dependent manner. PCP (10 mg/kg, i.p.) pro duced hyperlocomotion and stereotyped behaviors, including rearing, sniffing head-twitch, backpedalling and turning. Risperidone (0.8-2.4 mg/kg, p.o.) inhibited both hyperlocomotion and PCP-induced behaviors, except for backpedalling, while ritanserin (3 -10 mg/kg, p.o.) inhibited only the head-twitch. These results suggest that risperidone may have an antipsychotic effect on schizophrenia as well as PCP psychosis in humans by exerting a mixed 5-HT2A/D2 antagonism. Neurochemically, the increasing effects of risperidone on the content of DOPAC and the ratio of DOPAC to dopamine in the striatum were lower than those of haloperidol. These findings may support the view that the extrapyramidal side effects of risperidone are lower than those of haloperidol in clinical situations.

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Section: Discussionmentioning

confidence: 56%

Section: Measurementmentioning

confidence: 99%

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confidence: 99%

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Effects of Risperidone on Phencyclidine-Induced Behaviors: Comparison with Haloperidol and Ritanserin

Kitaichi

Yamada

Hasegawa

et al. 1994

Japanese Journal of Pharmacology

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“…Other than being a noncompetitive antagonist of the NMDA receptor, PCP is also an inhibitor of serotonin and dopamine reuptake and affects gamma-aminobutyric acid (GABA) neuronal function (Smith et al, 1977;Gerhardt et al, 1987). It is generally assumed that the rewarding effects of acute or chronic PCP treatment are related to an increase in mesolimbic extracellular dopaminergic levels (Di Chiara and Imperato, 1988;Carboni et al, 1989) and a dosedependent progressive downregulation of 5-HT 2A receptors in response to the elevation in serotonin turnover produced by the drug (Nabeshima et al, 1985(Nabeshima et al, , 1987Noda et al, 1998). Growing evidence indicates that PCP preferentially elevates dopaminergic transmission through its antagonist actions on NMDA receptors located on GABAegic inhibitory interneurons, thereby disinhibiting the firing of dopaminergic neurons, rather than through its action as a dopamine reuptake inhibitor (Jentsch et al, 1997a(Jentsch et al, , 1998a.…”

Section: Discussionmentioning

confidence: 99%

Withdrawal from Chronic Phencyclidine Treatment Induces Long-Lasting Depression in Brain Reward Function

Spielewoy

Markou

2002

Neuropsychopharmacol

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Phencyclidine (PCP) is a drug of abuse that has rewarding and dysphoric effects in humans. The complex actions of PCP, and PCP withdrawal in particular, on brain reward function remain unclear. The purpose of the present study was to characterize the effects of withdrawal from acute and chronic PCP treatment on brain reward function in rats. A brain stimulation reward procedure was used to evaluate the effects of acute PCP injection (0, 5, or 10 mg/kg) or chronic PCP treatment (0, 10, 15, or 20 mg/kg/day for 14 days delivered via subcutaneous osmotic minipumps) on brain reward function. Withdrawal from acute administration of 5 and 10 mg/kg PCP produced a decrease in brain reward function as indicated by a sustained elevation in brain reward thresholds. When administered chronically, 10, 15, or 20 mg/kg/day PCP induced a progressive dose-dependent potentiation of brain stimulation reward, while cessation of the treatment resulted in significant elevations in reward thresholds reflecting diminished reward. Specifically, withdrawal from 15 or 20 mg/ kg/day PCP induced a depression in brain reward function that lasted for the entire month of observation. These results indicate that prolonged continuous administration of high PCP doses facilitates brain stimulation reward, while withdrawal from acute high PCP doses or chronic PCP treatment results in a protracted depression of brain reward function that may be analogous to the dysphoric and anhedonic symptoms observed in PCP dependence, depression, and schizophrenia.

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“…Development of tolerance to the behavioural effects of PCP on operant responding (Balster & Chait, 1976;Chait & Balster, 1978;Murray, 1978;Woolverton & Balster, 1979), motor incoordination (Pinchasi et al, 1978a, b;Nabeshima et al, 1982a, b;Hiramatsu et al, 1984;Noda et al, 1995), and stereotyped behaviours (Sturgeon et al, 1982;Nabeshima et al, 1982a, b;1987;Kitaichi et al, 1995;Noda et al, 1995) increase in stereotyped behaviours in stumpai macaques (Schlemmer et al, 1978) and increased locomotor activity, stereotyped sniffing and rearing in rats (Smith et al, 1978;Nabeshima et al, 1987;Xu & Domino, 1994;Kitaichi et al, 1995). However, little is known about the mechanisms involved in the development of tolerance and sensitization to the effects of PCP.…”

Section: Introductionmentioning

confidence: 99%

Role of nitric oxide in the development of tolerance and sensitization to behavioural effects of phencyclidine in mice

Noda

Yamada

Komori

et al. 1996

British J Pharmacology

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1 To determine whether nitric oxide (NO) was involved in tolerance and sensitization to the effects of phencyclidine (PCP), we examined NO synthase activity and the number of NADPH-diaphorase (NADPH-d)-positive cells in discrete brain regions of saline-, acute PCP-and repeated PCP-treated mice. We also investigated the effects of a NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on the behavioural changes induced by repeated PCP treatment in mice. 2 Acute PCP (1, 3, and 10 mg kg-', s.c.) treatment induced dose-dependent hyperlocomotion, motor incoordination and stereotyped behaviours, consisting of sniffing, head movement and ataxia in mice. 3 In mice treated repeatedly with PCP (1, 3, and 10 mg kg-' day-'), s.c., once a day for 14 days), the sniffing, head movement, ataxia and motor incoordination induced by PCP were attenuated (indicating the development of tolerance to these behaviours), whereas the hyperlocomotion induced by PCP was potentiated (indicating the development of sensitization to hyperlocomotion). The development of tolerance and sensitization to PCP-induced behaviours in the repeated PCP-treated mice was more marked at the dose of 10 mg kg-' day-') than at other doses. 4 NO synthase activity in the cerebral cortex and cerebellum, but not in the striatum and hippocampus, was significantly decreased by acute PCP (10 mg kg-') treatment in comparison with saline treatment, and such changes in activity in the cerebral cortex and cerebellum were reversed by repeated PCP treatment (10 mg kg-' day-'). 5 The number of neurones containing NADPH-d reactivity in the cerebral cortex, nucleus accumbens, and striatum of acute and repeated PCP-treated mice showed no change in comparison with salinetreated mice. 6 Tolerance to PCP (10 mg kg-' day-')-induced ataxia and motor incoordination was significantly attenuated by combined treatment with L-NAME (50 mg kg-' day-' i.p.). 7 Sensitization to PCP-induced hyperlocomotion was further enhanced by combined treatment with L-NAME (50 mg kg-' day-'). However, NG-nitro-D-arginine methyl ester (D-NAME, 50 mg kg-' day-', i.p.), a less active enantiomer of L-NAME, had no effect, suggesting a stereospecific mechanism. 8 The PCP-induced behaviours in animals that had exhibited tolerance and sensitization to PCP (10 mg kg-' day-') were not influenced by acute L-NAME (5 and 50 mg kg-', i.p.) or D-NAME (50 mg kg-', i.p.) treatment. 9 These results suggest that NO may play an important role in the development, but not in the maintenance, of tolerance and sensitization to the effects of PCP in mice.

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

Cited by 69 publications

References 35 publications

Effects of Risperidone on Phencyclidine-Induced Behaviors: Comparison with Haloperidol and Ritanserin

Effects of Risperidone on Phencyclidine-Induced Behaviors: Comparison with Haloperidol and Ritanserin

Withdrawal from Chronic Phencyclidine Treatment Induces Long-Lasting Depression in Brain Reward Function

Role of nitric oxide in the development of tolerance and sensitization to behavioural effects of phencyclidine in mice

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