Interactions between dopamine D1 receptors and gamma-aminobutyric acid mechanisms in substantia nigra pars reticulata of the rat: neurochemical and behavioral studies.
BACKGROUND
Several studies have shown that dopamine D1 agonists act on forebrain dopamine terminal regions to exert many of their behavioral effects. Yet, there is also a large number of D1 receptors in the substantia nigra pars reticulata (SNr), and these receptors are located mainly on terminals of gamma-aminobutyric acid (GABA)-ergic striatonigral neurons.


OBJECTIVE
The present studies were undertaken to determine the behavioral and neurochemical effects of local administration of the D1 agonist SKF 82958 and to study the interactions between D1 and GABA mechanisms in SNr.


METHODS
Microdialysis methods were used to characterize the effect of SKF 82958 on extracellular GABA, and several experiments studied the effects of nigral D1 stimulation on motor activity and investigated the behavioral significance of D1/GABA interactions in SNr.


RESULTS
Local infusion of 10(-6) M SKF 82958 increased extracellular levels of SNr GABA, and this effect was blocked by co-infusion of the D1 antagonist SCH 23390. Bilateral SNr injections of SKF 82958 increased locomotor activity, and this effect was blocked by the GABA-A antagonist bicuculline. Intranigral bicuculline reduced motor activity, while the GABA-A agonist muscimol increased various motor activities in a manner similar to SKF 82958.


CONCLUSIONS
The present results suggest that the D1 agonist SKF 82958 acts on D1 receptors in SNr to increase extracellular levels of GABA, and the increase in motor activity produced by nigral D1 stimulation is dependent on stimulation of GABA-A receptors. D1/GABA interactions in SNr are important for the modulation of basal ganglia output, which may have important implications for Parkinson's disease.
Trevitt
T
T
Department of Psychology, University of Connecticut, Storrs, CT 06269-1020, USA.
Carlson
B
B
Correa
M
M
Keene
A
A
Morales
M
M
Salamone
J D
JD
D000818:Animals; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis* / Q000378:metabolism
D018491:Dopamine Agonists; D018755:GABA Agonists; D018756:GABA Antagonists; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D017447:Receptors, Dopamine D1; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid