Excitatory amino acids have been postulated to act as neurotransmitters and neuromodulators in the nucleus accumbens. When different excitatory amino acids agonists are microinjected into the nucleus accumbens, they produce a marked hypermotility response. The overall objective of these studies is to understand how these agonists interact with different neuronal systems in the nucleus accumbens in order to produce a coordinated locomotor response.
The specific aims are to determine 1) what role dopaminergic neurons in the nucleus accumbens play in the excitatory amino acid induced-hypermotility response. Thus, experiments will be performed to determine whether dopaminergic neurons are essential for the response and whether these neurons interact directly with excitatory amino acids, 2) whether excitatory amino acids interact with serotonergic cholinergic, GABAergic, and glutamatergic neurons in the nucleus accumbens and the possible role of this interaction in the hypermotility response, 3) whether the effects of excitatory amino acids are mediated through an interaction with excitatory amino acid receptors, 4) whether the hypermotility responses produced by different drugs that act in the nucleus accumbens are mediated by the same neuronal mechanisms, 5) whether the hypermotility responses produced by the intraccumbens administration of substances found endogenously such as folic acid derivatives, thyrotropin-releasing hormone and quinolinic acid are mediated through the activation of excitatory amino acid receptors, 6) whether the activation of excitatory amino acid receptors is involved in the mediation of the hypermotility response produced by conditions which activate the meso-limbic dopaminergic neurons. It has been postulated that excitatory amino acids act as neurotransmitters or neuromodulators in the nucleus accumbens. However, the identity of the excitatory amino acids and their functional actions at this site are not known. The studies of this proposal should provide insight into the functional role of excitatory amino acids in the nucleus accumbens.
