ANIMAL MODELS OF NEUROPSYCHIATRIC DISORDERS

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The microdialysis technique, for continuous in vivo sampling of extracellular fluid in anatomically specific brain sites, was established in our laboratory this year. Peripheral administration of haloperidol increased concentrations of DOPAC and HVA in the caudate nucleus, while peripheral administration of amphetamine decreased DOPAC and HVA in the nucleus accumbens as previously described, validating our methodology. Microinjection of nanomole quantities of cholecystokinin and of neurotension into the ventral tegmentum of rats was shown to increase DOPAC and HVA in the nucleus accumbens, for up to 2 hours. Intraventricular injection of antiserum from patients with Sydenham's Chorea produced a small, highly variable increase in DOPAC and HVA in the caudate nucleus of rats. Peripheral administration of alprazolam caused a potentiation of the effects of haloperidol on increasing DOPAC and HVA in the caudate nucleus and in the prefrontal cortex of the rat. Microinjection of apomorphine into the prefrontal cortex produced a significant decrease in DOPAC and HVA in the caudate nucleus of rats. Microdialysis in the awake, freely moving rat revealed a small increase in DOPAC and HVA in the nucleus accumbens during periods of hyperlocomotion in rats placed in a Digiscan activity monitor, as compared to periods of rest in a holding cage. The microdialysis technique appears to be useful for addressing many of the anatomical, biochemical, and behavioral hypotheses of dopaminergic mechanisms relevant to the etiology and treatment of schizophrenia.