Functional interaction of dopamine and glutamate in the nucleus accumbens in the regulation of locomotion.
The interaction of dopamine and glutamate in the nucleus accumbens in the regulation of locomotion was investigated. Microinjection of N-methyl-D-aspartic acid (NMDA, a glutamatergic NMDA receptor agonist) or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA, a quisqualic receptor agonist which is a glutamatergic non-NMDA receptor agonist) into the nucleus accumbens caused a substantial increase in locomotor activity. This increase in locomotor activity was significantly reduced by prior administration of the dopamine D2 agonist quinpirole, but not the D1 agonist, SKF 38393, into the same brain sites. The reduction in locomotion produced by quinpirole was dose dependent. Eight days after the ventral tegmental area was lesioned with 6-hydroxydopamine to destroy the dopamine projection and the axon terminals of the mesolimbic dopamine neurons in nucleus accumbens, the hyperkinetic effects produced by injections of NMDA and AMPA into the nucleus accumbens were substantially reduced. These results suggested that the glutamate agonist induced locomotion is mediated by dopamine. Thus, it appears that NMDA- or AMPA-induced locomotion is due to the activation of glutamate receptors on the mesolimbic dopamine terminals in the nucleus accumbens which release dopamine and subsequently increase locomotion.
Wu
M
M
Department of Physiology, University of Western Ontario, London, Canada.
Brudzynski
S M
SM
Mogenson
G J
GJ
D000818:Animals; D001927:Brain Diseases / Q000139:chemically induced / Q000503:physiopathology; D004298:Dopamine / Q000502:physiology*; D015259:Dopamine Agents / Q000494:pharmacology; D004873:Ergolines / Q000494:pharmacology; D005971:Glutamates / Q000502:physiology*; D018698:Glutamic Acid; D006948:Hyperkinesis / Q000139:chemically induced; D007276:Injections, Intraventricular; D008032:Limbic System / Q000502:physiology; D008124:Locomotion / Q000187:drug effects / Q000502:physiology*; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000502:physiology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D016627:Oxidopamine; D017729:Presynaptic Terminals / Q000502:physiology; D019257:Quinpirole; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D015259:Dopamine Agents; D004873:Ergolines; D005971:Glutamates; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D018698:Glutamic Acid; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D016627:Oxidopamine; D004298:Dopamine