Acetylcholine release in rat nucleus accumbens is regulated through dopamine D2-receptors.
Experiments in slices of rat nucleus accumbens were carried out in order to investigate whether the release of acetylcholine in this tissue is modulated through dopamine receptors. The slices were preincubated with 3H-choline and then superfused and stimulated electrically twice for 2 min each at a frequency of 3 Hz. The electrically evoked overflow of tritium averaged 2.9-3.9% of the tritium content of the tissue in the various groups. The D2-selective agonist quinpirole (0.01-1 mumol/l) reduced the evoked overflow of tritium by maximally 56%, an effect antagonized by the D2-selective antagonist (-)-sulpiride (1 mumol/l). The D1-selective agonist 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine (SKF 38393) caused a slight decrease only at the high concentration of 10 mumol/l. (-)-Sulpiride (0.1-10 mumol/l) moderately increased the evoked overflow of tritium when given alone. The dopamine uptake inhibitor nomifensine (10 mumol/l) caused a decrease, and in its presence the increase produced by (-)-sulpiride became much more marked, amounting to maximally 149% (+)-Sulpiride (0.1-1 mumol/l) failed to change the evoked overflow of tritium in the presence of nomifensine. The dopamine-releasing agent (+/-)-amphetamine (1 mumol/l) also reduced the evoked overflow, an effect abolished by (-)-sulpiride. Finally, bretylium (1 mmol/l), which blocks the release of dopamine, increased the evoked overflow. (-)-Sulpiride (1 mumol/l) lost its facilitatory effect in slices treated with bretylium. We conclude that the release of acetylcholine in rat nucleus accumbens, like its release in the nucleus caudatusputamen, is modulated through dopamine D2-receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Wedzony
K
K
Pharmakologisches Institut, Freiburg i.Br., Federal Republic of Germany.
Limberger
N
N
Späth
L
L
Wichmann
T
T
Starke
K
K
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000109:Acetylcholine / Q000378:metabolism*; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001949:Bretylium Compounds / Q000494:pharmacology; D002794:Choline / Q000494:pharmacology; D004558:Electric Stimulation; D004873:Ergolines / Q000494:pharmacology; D008297:Male; D009627:Nomifensine / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000378:metabolism*; D019257:Quinpirole; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism*; D012686:Septal Nuclei / Q000378:metabolism*; D013469:Sulpiride / Q000494:pharmacology
D001552:Benzazepines; D001949:Bretylium Compounds; D004873:Ergolines; D011954:Receptors, Dopamine; D009627:Nomifensine; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D013469:Sulpiride; D000661:Amphetamine; D002794:Choline; D000109:Acetylcholine; C045166:bretylium