Antipsychotic drugs dose-dependently suppress the spontaneous hyperactivity of the chakragati mouse.
The chakragati (ckr) mouse has been proposed as a model of aspects of schizophrenia. The mice, created serendipitously as a result of a transgenic insertional mutation, exhibit spontaneous circling, hyperactivity, hypertone of the dopamine system, reduced social interactions, enlarged lateral ventricles, deficits in pre-pulse inhibition of acoustic startle and deficits in latent inhibition of conditioned learning. In this study, the dose-dependent effects of antipsychotic drugs (haloperidol, pimozide, risperidone, clozapine, olanzapine, ziprasidone, quetiapine and aripiprazole) on the spontaneous hyperactivity of the mice were investigated. All the antipsychotic drugs tested dose-dependently suppressed spontaneous hyperactivity. Aripriprazole, which is known to be a dopamine D2 receptor partial agonist, exhibited a tri-phasic dose-response, initially suppressing hyperactivity at low doses, having little effect on hyperactivity at intermediate doses, and suppressing activity again at high doses. These data suggest that the spontaneous circling and hyperactivity of the ckr mouse may allow screening of candidate antipsychotic compounds, distinguishing compounds with aripriprazole-like profiles.
Dawe
G S
GS
Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System and Neurobiology and Ageing Programme, Centre for Life Sciences, National University of Singapore, 28 Medical Drive, Singapore 117456. gavindawe@nus.edu.sg
Nagarajah
R
R
Albert
R
R
Casey
D E
DE
Gross
K W
KW
Ratty
A K
AK
D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006948:Hyperkinesis / Q000188:drug therapy* / Q000209:etiology*; D007266:Inhibition, Psychological; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism; D012559:Schizophrenia / Q000150:complications* / Q000188:drug therapy / Q000235:genetics
D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin