Effects of excitatory amino acids on locomotor activity after bilateral microinjection into the rat nucleus accumbens: possible dependence on dopaminergic mechanisms.

In order to study the role of excitatory amino acids on motor function, the effects of kainic, quisqualic, and N-methyl-DL-aspartic acids on locomotor activity were determined after their direct injection into the nucleus accumbens. These three amino acids have been used in previous studies to classify receptors for excitatory amino acids in the mammalian spinal cord. After injection into the nucleus accumbens all three amino acids stimulated locomotor activity, with kainic acid being the most potent and N-methyl-DL-aspartic acid the least potent. The maximum intensity of the stimulation produced by kainic and quisqualic acids was greater than that produced by N-methyl-DL-aspartic acid. These results suggest that receptors in the nucleus accumbens, sensitive to kainic and quisqualic acids, play a more important role in the stimulation of locomotor activity than those sensitive to N-methyl-DL-aspartic acid. In addition to the above amino acids, the administration of large doses of L-aspartic and D-glutamic acids also produced hyperactivity, while L-glutamic acid had no effect. To determine whether endogenous dopamine mediates the hypermotility produced by the excitatory amino acids, the response to these amino acids was studied after treatment with reserpine or dopamine receptor blocking agents. Reserpine (5 mg/kg, i.p.), haloperidol (0.8 mg/kg, i.p.) or fluphenazine [5.0 micrograms (total dose) injected into the nucleus accumbens] markedly attenuated the hypermotility induced by excitatory amino acids. These results suggest that the hypermotility produced by excitatory amino acids is mediated through release of dopamine and the subsequent stimulation of dopamine receptors in the nucleus accumbens.