Effects of dopaminergic drugs on phencyclidine-induced behavior in the rat

Castellani, Sam; Adams, Perrie M.

doi:10.1016/0028-3908(81)90011-3

Cited by 60 publications

(13 citation statements)

References 19 publications

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“…Psychomotor stimulants are known to increase dopamine transmission in the striatum (Carboni et al, 1989;Johnson, 1983;Seiden et al, 1993;Steinpreis and Salamone, 1993), and our results with haloperidol and clozapine support ample behavioral evidence for an underlying dopaminergic mechanism (Castellani and Adams, 1981;French and Vantini, 1984;Kameyama et al, 1988;Murray and Horita, 1979;Sturgeon et al, 1981). In fact, our behavioral data suggest that typical and atypical neuroleptics are equally effective in blocking a wide range of PCP-induced open-field behaviors.…”

Section: Discussionsupporting

confidence: 83%

Phencyclidine-induced increases in striatal neuron firing in behaving rats: reversal by haloperidol and clozapine

White

Flory

Hooper

et al. 1995

J. Neural Transmission

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Amphetamine and related drugs of abuse facilitate dopamine transmission in the striatum. This action is believed to underlie the increase in firing of striatal motor-related neurons after amphetamine administration in behaving rats. The present study extended this electrophysiological investigation to phencyclidine (PCP), a nonamphetamine psychomotor stimulant that acts primarily as a noncompetitive antagonist of N-methyl-D-aspartate (NMDA) glutamate receptors. Like amphetamine, PCP (1.0, 2.5, or 5.0 mg/kg) increased the activity of striatal motor-related neurons concomitant with behavioral activation. These effects were blocked by subsequent administration of either 1.0 mg/kg haloperidol or 20.0 mg/kg clozapine, typical and atypical neuroleptics, respectively. Dizocilpine (MK- 801), another noncompetitive NMDA antagonist, mimicked the effect of PCP. Collectively, these results indicate that amphetamine and NMDA antagonists exert comparable effects on striatal motor-related neurons, suggesting that the response of these cells to psychomotor stimulants is regulated by a dopaminergic-glutamatergic influence.

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Section: Discussionsupporting

confidence: 83%

Phencyclidine-induced increases in striatal neuron firing in behaving rats: reversal by haloperidol and clozapine

White

Flory

Hooper

et al. 1995

J. Neural Transmission

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“…Although extrapolation of data from rodent models to complex human syndromes such as PCP psychosis or schizophrenia may be problematic, hyperlocomotion in rodents has been generally used as a predictor of the propensity of a drug to elicit or exacerbate psychosis in humans (Castellani & Adams, 1981;Greenburg & Segal, 1985;French, 1986;Carlsson et al, 1993;Jackson et al, 1994;Ogren & Goldstein, 1994;Steinpreis et al, 1994;Krystal et al, 1995;Goldman-Rakic, 1996;Verma & Moghaddam, 1996;Moghaddam & Adams, 1998). Therefore, the ability of a compound to antagonise PCP-induced behaviour and neuronal activation would be predictive of its antipsychotic properties in humans.…”

Section: Discussionmentioning

confidence: 99%

Blockade of phencyclidine‐induced effects by a nitric oxide donor

Bujas‐Bobanovic

Bird

Robertson

et al. 2000

British J Pharmacology

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1 Phencyclidine (PCP) is widely used as an animal model of schizophrenia. The aim of this study was to better understand the role of nitric oxide (NO) in the mechanism of action of PCP and to determine whether positive NO modulators may provide a new approach to the treatment of schizophrenia. 2 The eects of the NO donor, sodium nitroprusside (SNP), were studied in PCP-treated rats. Following drug administration, behavioural changes and the expression of c-fos, a metabolic marker of functional pathways in the brain, were simultaneously monitored. 3 Acute PCP (5 mg kg 71 , i.p.) treatment induced a complex behavioural syndrome, consisting of hyperlocomotion, stereotyped behaviours and ataxia. Treatment with SNP (2 ± 6 mg kg 71 , i.p.) by itself produced no eect on any behaviour studied but completely abolished PCP-induced behaviour in a dose-and time-dependent manner. 4 PCP had dierential regional eects on c-fos expression in rat brain, suggesting regionally dierent patterns of neuronal activity. The most prominent immunostaining was observed in the cortical regions. Pre-treatment with SNP blocked PCP-induced c-fos expression at doses similar to those that suppress PCP-induced behavioural eects. 5 These results implicate the NO system in the mechanism of action of PCP. The fact that SNP abolished eects of PCP suggests that drugs targeting the glutamate-NO system may represent a novel approach to the treatment of PCP-induced psychosis and schizophrenia.

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“…Ketamine is a structural analogue of PCP, which binds to the PCP site of the NMDA receptor with about one tenth the potency of PCP (Kornhuber and Weller 1995). At higher doses ketamine, like PCP, has broader neurochemical actions (Tonge and Leonard 1969;Raja and Guyenet 1980;Castellani and Adams 1981;Nabeshima et al 1981;Malare et al 1982). Ketamine is made of a racemic mixture with the S-enantioner displaying a 3-4 higher affinity for the NMDA receptor than the R-ketamine (Oye et al 1991).…”

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confidence: 99%