Release of acetylcholine and its dopaminergic control in slices from striatal grafts in the ibotenic acid-lesioned rat striatum.
Tritium accumulation during incubation with 3H-choline, and the efflux as well as the electrically evoked overflow of tritium during subsequent superfusion, were investigated in slices from unilateral striatal suspension grafts 16 to 20 weeks after implantation into the previously ibotenic acid-lesioned rat striatum. Slices from non-operated animals, from striata contralateral to grafts, and from animals with acute ibotenic acid lesions of the striatum were studied in parallel. The accumulation of tritium and the overflow of tritium in response to electrical stimulation (2 min, 3 Hz) were markedly impaired in acutely lesioned striata. In graft slices, tritium accumulation and the subsequent electrically evoked overflow were greater than in slices obtained after acute lesions, but were still smaller than in non-operated animals or in the contralateral striata. The dopamine D2-receptor agonist quinpirole inhibited the electrically evoked overflow of tritium in grafts, but only to a small extent. The D2-receptor antagonist sulpiride increased, whereas the dopamine uptake inhibitor nomifensine and the dopamine releasing drug amphetamine decreased the evoked overflow in slices from non-operated rats and from striata contralateral to grafts, but had no significant effect in grafts. As in graft slices, the release of acetylcholine in striata from animals in which the mesostriatal dopamine pathway had been lesioned by 6-hydroxy-dopamine was not changed by sulpiride and amphetamine, and was only minimally decreased by nomifensine. Our data show that striato-striatal grafts can partly restore the impaired choline accumulation and acetylcholine release in excitotoxin-lesioned striata. Functional D2-receptors are present on graft cholinergic cells, but are not activated by endogenous dopamine under the present in vitro conditions.
Wichmann
T
T
Institute of Pharmacology, University of Freiburg, Federal Republic of Germany.
Wictorin
K
K
Björklund
A
A
Starke
K
K
D000109:Acetylcholine / Q000378:metabolism*; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000637:transplantation; D004298:Dopamine / Q000502:physiology*; D004873:Ergolines / Q000494:pharmacology; D006892:Hydroxydopamines / Q000494:pharmacology; D007051:Ibotenic Acid / Q000494:pharmacology*; D066298:In Vitro Techniques; D009627:Nomifensine / Q000494:pharmacology; D010080:Oxazoles / Q000494:pharmacology*; D016627:Oxidopamine; D019257:Quinpirole; D051381:Rats; D011919:Rats, Inbred Strains; D013469:Sulpiride / Q000494:pharmacology; D014184:Transplantation, Homologous
D004873:Ergolines; D006892:Hydroxydopamines; D010080:Oxazoles; D009627:Nomifensine; D019257:Quinpirole; D007051:Ibotenic Acid; D013469:Sulpiride; D016627:Oxidopamine; D000661:Amphetamine; D000109:Acetylcholine; D004298:Dopamine