Animal models of psychosis

Do animal models of psychosis select antipsychotic drugs reliably ... 

The principle animal model of psychosis has for many years been the hyperactivity and stereotypies induced by stimulant drugs. In animals... 

Numerous other animal models of psychosis have been proposed, but few others have been used routinely for drug screening. The model called the conditioned avoidance response is considered important, however. Smith and colleagues describe the test as follows ... 

Cannabidiol Attentuated apomorphine-induced stereotypy in animal model of psychosis-similar to effect of other antipsychotic drugs. Animal study showed increased prolactin secretion similar to described antipsychotic effect. Based on observed effects, mechanism of action may be similar to atypical antipsychotics, though no data available on specific neurotransmitters involved. 

Robinson, T.E., and Becker, J.B. Enduring changes in brain and behavior produced by chronic amphetamine administration A review and evaluation of animal models of amphetamine psychosis. Brain Res 11 157-198, 1986. 

Ellinwood, E.H., Jr., and Kilbey. M.M. Chronic stimulant intoxication models of psychosis. In Hanin, I., and Usdin, E., eds. Animal Models in Psychiatry and Neurology. New York Pergamon Press, 1977. pp. 61-74. 

The close resemblance between schizophrenia and PCP-induced psychosis suggests that the behavioral effects produced by PCP might be useful as a model of psychosis. On this basis, most animal studies have examined the ability of various agents to modify PCP-induced hyperactivity and stereotypy. While some studies suggest that neuroleptics such as haloperidol (Castellani and Adams 1981 Garey et al. 1980), chlorpromazine, or clozapine (Freed et al. 

Segal, D. S., and Schuckit, M. A. (1983). Animal models of stimulant-induced psychosis. In Stimulants Neurochemical, Behavioral and Clinical Perspectives (I. Grees, ed.), pp. 131-167. Reven, New York. 

Rujescu D, Bender A, Keck M, Hartmann AM, Ohl F, Raeder H, Giegling I, Genius J, McCarley RW, Moller HJ, Grunze H. A pharmacological model for psychosis based on N-methyl-D-aspartate receptor hypofunction molecular, cellular, functional and behavioral abnormalities. Biol. Psychiatry 2006 59 721-729. Mouri A, Noda Y, Enomoto T, Nabeshima T. Phencyclidine animal models of schizophrenia approaches from abnormality of glutamatergic neurotransmission and neurodevelopment. Neu-rochem. Int. 2007 51 173-84. 

Several diverse, potent, and selective GlyT-1 inhibitors have appeared in the literature and many are reported to be efficacious in animal psychosis models. Several of these have advanced into Phase I and Phase II clinical studies. Recent Phase II results from a double-blind, 320-patient study with the investigational GlyT-1 inhibitor RG1678 (33) [17] demonstrated that the compound improved negative symptoms and social functioning of stable patients currently on atypical antipsychotic therapy and was well tolerated at all doses tested [18]. 

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