Striatal dopamine (DA) has been implicated in the regulation of locomotor activity reward processes and information processing, and thus may be involved in various psychomotor/psychiatric disorders, including among others, schizophrenia and dementia. Adenosine has been shown to modulate neuronal function in various central nervous systems regions, including the striatum, through a variety of receptor-mediated mechanisms involving second messenger systems, ion fluxes, and modulation of transmitter release. Alkylxanthines, such as caffeine, act as competitive antagonists at adenosine receptors. Recent work in our laboratory has shown that microinjections of selective adenosine A2a receptor agonists into either the dorsal striatum (i.e., caudate-putamen, CPU) or ventral striatum (i.e., nucleus accumbens, ACB) potently suppress locomotor activity while producing a differential effect on stereotyped behavior. In contrast, microinjections of selective adenosine A1 receptor agonists into either the ACB or CPU potently impaired memory of an inhibitory avoidance task. In light of numerous studies indicating that the striatum exhibits high A2a and A1 receptor density, as well as the existence of a functional linkage between adenosine and DA receptors, the present studies were designed to: (1) further examine the role of endogenous adenosine in the ACB and CPU in the processes mediating locomotor activity and information processing, and (2) compare and contrast the nature of the interaction between adenosine and DA receptor function within the ACB CPU in these processes. Specifically, the proposed studies will assess the effects of both central (intra-ACB vs intra-CPU) and peripheral drug administrations designed to alter adenosinergic, dopaminergic, and combined adenosinergic and dopaminergic receptor function, on locomotor activity and inhibitory avoidance memory. The results of these behavioral studies may shed light on the neuromolecular mechanisms involved in the etiology of certain mental health-related neurobehavioral disorders wherein a dysfunction in dopaminergic neurotransmission has been implicated, and may stimulate the development of novel pharmacological treatment strategies.
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