Electrophysiological evidence for the existence of both D-1 and D-2 dopamine receptors in the rat nucleus accumbens.
Extracellular single-unit recording and microiontophoretic techniques were used to characterize the pharmacological properties of dopamine (DA) receptors within the rat nucleus accumbens (NAc), a forebrain structure that receives a dense innervation from mesolimbic DA-containing neurons (A10 DA neurons) located in the ventral tegmental area (VTA). Of the NAc neurons tested, 75% were inhibited by microiontophoretic administration of the selective D-2 receptor agonist, LY-141865, whereas 38% were inhibited by microiontophoretic administration of the selective D-1 receptor agonist, SKF-38393. Of the 30 NAc neurons that were tested with both of these agonists, nine were inhibited by both agonists, 11 were inhibited only by LY-141865, five were inhibited only by SKF-38393, and five were not affected by either of these compounds. The inhibitory effects of LY-141865 were blocked and reversed by either intravenous or iontophoretic administration of the selective D-2 antagonist (-)-sulpiride, which, however, failed to alter the inhibitory effects of SKF-38393. In contrast, the purportedly selective D-1 antagonist, SCH-23390, selectively blocked and reversed the inhibitory effects of SKF-38393, suggesting that the two agonists were producing their inhibitory effects via distinct DA receptors. Additional experiments indicated that intravenous administration of LY-141865 caused a biphasic increase/decrease in the activity of NAc neurons. The initial rate increase was apparently due to disinhibition since it was also shown that D-2 DA receptors located on A10 DA neurons exhibited a 3-10-fold greater sensitivity to LY-141865 and DA as compared to the NAc D-2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
White
F J
FJ
Wang
R Y
RY
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D004873:Ergolines / Q000008:administration & dosage / Q000494:pharmacology; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D007276:Injections, Intraventricular; D007478:Iontophoresis; D008297:Male; D009714:Nucleus Accumbens / Q000032:analysis*; D019257:Quinpirole; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000032:analysis*; D012686:Septal Nuclei / Q000032:analysis*
D001552:Benzazepines; D004873:Ergolines; D005971:Glutamates; D011954:Receptors, Dopamine; D019257:Quinpirole; D018698:Glutamic Acid; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine