The release of dopamine from nerve terminals and dendrites of nigrostriatal neurons induced by excitatory amino acids in the conscious rat

Abstract

The possible localization of excitatory amino acid (EAA) receptors on dopaminergic neurons was studied by microdialysis in conscious male rats. Varying concentrations of 3 specific EAA agonists, N-methyl-D-aspartate (NMDA), kainate and amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), were infused into the striatum or into the substantia nigra, and the extracellular dopamine (DA) was recorded by the same probe. All 3 compounds induced a dose-dependent increase in both striatal and nigral extracellular DA. Kainate and AMPA were more potent than NMDA. Nigral DA release was stimulated by lower concentrations of kainate and AMPA than striatal DA release. The effects of two concentrations of NMDA and kainate on the release of DA were analyzed in terms of tetrodotoxin (TTX) dependency and sensitivity to ibotenic acid-induced striatal lesion. It appeared that NMDA and kainate stimulated DA release by 3 different mechanisms. The first mechanism is seen at low concentrations of kainate, it fulfills the criteria for a functional receptor-interaction: it is TTX-sensitive and independent of the ibotenic acid lesion. The second mechanism was observed when relatively low concentrations of NMDA stimulate the release of DA; in this effect postsynaptic structures are involved. The third mechanism lacks specificity as it is seen after high concentrations of kainate as well as of NMDA. The latter mechanism is TTX-independent and is probably of a toxic nature. Finally NMDA and kainate were infused into the nigra, whereas DA was recorded with a second probe implanted into the striatum.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrical Stimulation of the Medial Prefrontal Cortex Increases Dopamine Release in the Striatum

“…At higher concentrations (10-5 to 10-3 mollL), this effect was reversed, with DA release being decreased Leviel et al 1990). In vivo microdialysis experiments also support the facili tation of striatal DA release following a local injection of excitatory amino acids (Westerink et al 1992, Keefe et al 1992, although depression of DA release was not observed even at the highest concentrations used (1 mmol AMP A, 1 mmol N-methyl-D-aspartate, 0.1 mM kainate). These results show primarily, although not exclusively, facilitatory actions of glutamate on DA re lease in the striatum.…”

Dopamine D4 Receptor-Knock-Out Mice Exhibit Reduced Exploration of Novel Stimuli

“…Rather, D4Rs are densely localized on glutamatergic pyramidal cells of frontal cortex (Mrzljak et al, 1996;Ariano et al, 1997;Rubinstein et al, 1997) that project to the dorsal striatum and the substantia nigra (Carter, 1982). The stimulation of nigrostriatal nerve terminals (Westerink et al, 1992) in the dorsal striatum or of nigral neurons by glutamate induces dopamine release (Overton and Clark, 1992). Accordingly, dopamine synthesis and its conversion to DOPAC are increased in the dorsal striatum of D4RϪ/Ϫ mice (Rubinstein et al, 1997).…”

Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex

“…Another may be differences in the manner in which glutamate, released by these antagonists, may stimulate the release of dopamine in the PFC versus the striatum. Previous studies investigating this interaction indicate that stimulation of kainate or AMPA receptors is much more potent in increasing dopamine release in the PFC as compared with the striatum (Westerink et al, 1992;Jedema and Moghaddam, 1996).…”