The effect of intrastriatal application of directly and indirectly acting dopamine agonists and antagonists on the in vivo release of acetylcholine measured by brain microdialysis. The importance of the post-surgery interval.
The effect of intrastriatal application of D-1, D-2 and indirect dopaminergic drugs on the release of striatal acetylcholine as a function of the post-implantation intervals was studied using in vivo microdialysis. The dopamine D-2 agonists LY 171555 and (-)N0437 inhibited the release of striatal acetylcholine to 40% of control values 16-24 h after implantation of the dialysis cannula. When LY 171555 was infused 40-48 h after implantation of the dialysis cannula, the response was attenuated to 20% of control values. Meanwhile, the effectiveness of infusions of the antagonists (-)sulpiride and haloperidol was augmented from a non significant effect at 16-24 h to a 150% increase 40-48 h after implantation of the cannula. Infusions of the dopamine releasing agent amphetamine or the dopamine uptake inhibitor nomifensine resulted in a dose-dependent increase in the overflow of dopamine. Not until a sevenfold increase in the level of dopamine was seen, the release of acetylcholine was significantly affected. This hyporesponsiveness of the striatal cholinergic interneurons to endogenous dopamine could not be attributed to dopamine D-1 receptor activation, since no effects on striatal acetylcholine release were found by intrastriatal infusions of the selective D-1 agonist CY 208-243 or the selective D-1 antagonist SCH 23390. The results indicate that dopamine D-2 receptors are involved in the regulation of striatal acetylcholine release and that these receptors are tonically occupied by endogenous dopamine under the present experimental conditions 40-48 h after probe implantation.(ABSTRACT TRUNCATED AT 250 WORDS)
De Boer
P
P
Department of Medicinal Chemistry, University of Groningen, The Netherlands.
Damsma
G
G
Schram
Q
Q
Stoof
J C
JC
Zaagsma
J
J
Westerink
B H
BH
D000109:Acetylcholine / Q000378:metabolism*; D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000502:physiology*; D015259:Dopamine Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018492:Dopamine Antagonists; D004873:Ergolines / Q000008:administration & dosage / Q000494:pharmacology; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D016627:Oxidopamine / Q000494:pharmacology; D010617:Phenanthridines / Q000008:administration & dosage / Q000494:pharmacology; D019257:Quinpirole; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013469:Sulpiride / Q000008:administration & dosage / Q000494:pharmacology
D001552:Benzazepines; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D004873:Ergolines; D007211:Indoles; D010617:Phenanthridines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C054531:CY 208-243; D019257:Quinpirole; D013469:Sulpiride; D016627:Oxidopamine; D000661:Amphetamine; D006220:Haloperidol; D000109:Acetylcholine; D004298:Dopamine