Journal of Neuroscience, Vol 13, 4272-4280, Copyright © 1993 by Society for Neuroscience
Intraneostriatal administration of glutamate antagonists increases behavioral activation and decreases neostriatal ascorbate via nondopaminergic mechanisms
RC Pierce and GV Rebec
Department of Psychology, Indiana University, Bloomington 47405.
Behavioral findings suggest that the effects of neostriatal glutamate and
ascorbate are opposed to those of neostriatal dopamine. Recent evidence
also indicates that glutamate and ascorbate are linked via a
carrier-mediated heteroexchange process, suggesting that ascorbate may act
through the glutamate system to influence behavior. In order to assess
glutamate-ascorbate interactions and their influence on the behavioral
output of the basal ganglia, glutamate and homocysteic acid (a glutamate
reuptake blocker) as well as NMDA antagonists were infused into the
neostriatum of freely moving rats while extracellular neostriatal ascorbate
was monitored via electrochemically modified carbon-fiber electrodes.
Neostriatal 3,4-dihydroxyphenylacetic acid (DOPAC), a major dopamine
metabolite, also was recorded in order to assess the dependency of any drug
effect on the nigrostriatal dopamine system. Intraneostriatal infusions of
L-glutamate (1 micrograms/microliters), but not L-homocysteic acid (30
micrograms/microliters), elevated extracellular neostriatal ascorbate
levels. Neither of these drugs had any effect on neostriatal DOPAC or overt
behavioral activity. Intraneostriatal infusion of the noncompetitive NMDA
antagonist dizocilpine (MK-801; 3 micrograms/microliters) or the
competitive NMDA antagonist 3-(2-
carboxypiperazin-4-yl)-propyl-1-phosphonene (CPPene; 5
micrograms/microliters) decreased neostriatal ascorbate but had no effect
on neostriatal DOPAC. Both dizocilpine and CPPene activated behavior in
intact and sham-lesioned animals as well as in animals with near-total
depletions of neostriatal dopamine following a 6- hydroxydopamine lesion.
When administered systemically, however, dizocilpine (1.0 mg/kg)
significantly increased neostriatal DOPAC. This effect appears to be
regulated via midbrain NMDA receptors, in that this effect was completely
abolished by electrolytic lesions of the substantia nigra pars
reticulata.(ABSTRACT TRUNCATED AT 250 WORDS)