Effect of Cocaine Self-Administration on Metabotropic Glutamate Systems

Wake Forest University Health Sciences, Winston-Salem NC

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Abstract

DESCRIPTION (provided by applicant): Research into the role of neurotransmitter systems in the reinforcing effects of cocaine has traditionally focused on monoamines;however recent studies in rodents indicate a strong involvement of glutamatergic mechanisms, particularly during abstinence. Glutamate is an important transmitter due to its prominent role in synaptic plasticity and the remodeling of synapses. We have previously demonstrated significant alterations within the dopamine system of nonhuman primates following chronic cocaine self-administration and abstinence. Given the close reciprocal association between the dopamine and glutamate systems, we hypothesize, therefore, that the glutamate system in these monkeys is also significantly dysregulated. These hypotheses are supported by evidence from animal studies demonstrating direct effects of chronic cocaine exposure and abstinence on the glutamate system. We propose to test these hypotheses by measuring the concentrations of metabotropic glutamate receptors in monkeys previously studied. Thus, one of the significant advantages of the present application is our ability to relate any changes observed in the glutamate system back to previous findings of neurochemical dysregulation in the same animals. The dopamine and glutamate systems have been shown to be closely related to each other in terms of reciprocal regulation. Changes in one system can have significant consequences for regulation of the other. This application will test the hypotheses that elements of the glutamate system is altered in nonhuman primates self-administering cocaine, followed by abstinence, in which the dopamine system has already been extensively characterized, and shown to be substantially dysregulated.