Neuroanatomically, neurochemically, and pharmacologically, the dopaminergic systems are among the most thoroughly neurotransmitter systems of the brain. Yet their behavioral significance, particularly in primates, is little understood. This project will investigate the role of dopamine (DA) in the brain's control of primate behavior by 1) monitoring the behavioral effects of intracerebral dopamine injections (IC-DA) in seven different sites in the caudate nucleus, putamen, amygdala, and substantia nigra and 2) testing whether DA receptors mediate the behavioral responses to IC-DA. Behavioral effects will be measured in young adult male long-tailed macaques (Macaca fascicularis) after bilateral intracerebral drug or sham treatment. Each of 42 monkeys will undergo a series of trials to determine the effects of IC-DA at one of seven sites. Subsequently, a previously tested site in the nucleus accumbens will be used in each monkey to address specific pharmacological questions concerning the IC-DA effects: 1) What are the dose-response curves for IC-DA effects and for their attenuation by intracerebral injections of a DA-receptor antagonist? 2) Do other DA agonists and antagonists produce similar effects? 3) Can intracerebrally injected agonists of other receptors elicit comparable effects? 4) Can antagonist of other receptors attenuate the response to IC-DA? 5) What is the time-course of IC-CA's effects, and are they due to residual quantities of the injected drugs or to state-dependent learning? 6) How does IC-DA in nucleus accumbens affect behavior in a novel environment? Delicate methods of intracerebral injection and a computer system for detailed coding of behavior, both developed in this laboratory, will be employed. After behavioral testing, the injection sites in each monkey will be histologically confirmed and terminal experiments to evaluate the distribution of IC-DA in the brain will be conducted. The long-term objective of this research is to elucidate the role of the striatum in primate behavior. Its relevance to medicine lies in the close relation between the central dopaminergic and other neurotransmitter systems and disorders of mental health.
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| Dubach, M; Schmidt, R; Kunkel, D et al. (1987) Primate neostriatal neurons containing tyrosine hydroxylase: immunohistochemical evidence. Neurosci Lett 75:205-10 |
