Modulation of the mesolimbic dopamine system by glutamate : Role of NMDA receptors

• Published in: Journal of neurochemistry Vol. 73; no. 2; pp. 839 - 848
• Main Author: KRETSCHMER, B. D
• Format: Journal Article
• Language: English
• Published: Oxford Blackwell 01.08.1999
• Subjects: 2-Amino-5-phosphonovalerate - analogs & derivatives; 2-Amino-5-phosphonovalerate - pharmacology; 3,4-Dihydroxyphenylacetic Acid - analysis; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid - pharmacology; Animals; Behavior, Animal - drug effects; Binding, Competitive - physiology; Biological and medical sciences; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Dizocilpine Maleate - pharmacology; Dopamine - analysis; Dopamine - metabolism; Excitatory Amino Acid Agonists - pharmacology; Excitatory Amino Acid Antagonists - pharmacology; Fundamental and applied biological sciences. Psychology; Glutamic Acid - pharmacology; Homovanillic Acid - analysis; Limbic System - chemistry; Limbic System - drug effects; Limbic System - metabolism; Male; mesolimbic system; Microdialysis; Motor Activity - drug effects; N-Methylaspartate - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate - agonists; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Receptors, N-Methyl-D-Aspartate - metabolism; Ventral Tegmental Area - chemistry; Ventral Tegmental Area - drug effects; Ventral Tegmental Area - metabolism; Vertebrates: nervous system and sense organs; Dopamine; Rat; Rodentia; Central nervous system; Glutamate receptor; Catecholamine; Glutamate; Locomotion; Vertebrata; Mammalia; Excitatory aminoacid; Neurotransmitter; NMDA receptor; Ventral tegmental area; Brain (vertebrata)
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.1999.0730839.x

Glutamate has been shown to modulate motor behavior, probably via N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors that are involved in the control of the mesolimbic dopamine (DA) system, that is, the ventral tegmental area (VTA)-nucleus accumbens (NAC). In the present study, we investigated the effects of uncompetitive (MK-801) and competitive [DL-2-amino-5-phosphonopentanoic acid (AP-5), CGP 40116] NMDA receptor antagonists and NMDA and AMPA on DA release in the mesolimbic system and on motor behavior. Systemic injection and intrategmental infusion of MK-801 increased DA levels in the VTA, but the systemic administration enhanced DA exclusively in the NAC and increased motor behavior. In contrast, intrategmental infusion of AP-5, but not the systemic administration of its lipophilic analogue CGP 40116, decreased the DA release in the two regions without affecting motor behavior. NMDA and AMPA infusion into the VTA increased DA levels in both areas. This increase was accompanied by a strong motor behavioral stimulation after NMDA but only a moderate increase after AMPA infusion. The present results indicate that mesolimbic DA neurons are controlled by the glutamatergic system and that the effects of uncompetitive and competitive NMDA receptor antagonists on DA release are mediated by an interaction with different brain areas. These findings may account for the different effects of NMDA receptor ligands on motor behavior.