Acetylcholine release in vivo: effects of chronic treatment with monosialoganglioside GM1.
Rats with unilateral cortical devascularizing lesions were treated with the monosialoganglioside GM1 in two different ways. One group of animals received GM1 (5 mg/kg/day, for 7 days), through a permanent cannula implanted intracerebroventricularly (i.c.v.) and connected to an osmotic minipump. The other group was treated with microencapsulated GM1 placed directly onto the surface of the lesioned cortex. The effect of GM1, administered into the lateral ventricle and supracortically, on the release of ACh in vivo was studied, using a microdialysis system combined with sensitive high performance liquid chromatography (HPLC). The release of acetylcholine and choline was studied in the cortex and striatum of the rat under nonstimulated (basal) and KCl (100 mM)-stimulating conditions. The non-stimulated release of acetylcholine was only measurable in the presence of neostigmine and was found to be about 30 microM in the cortex and approximately 10 times greater in the striatum. A large concentration of KCl led to a remarkable increase of acetylcholine in the control (C) and vehicle-treated lesioned groups (V i.c.v., V cap: 11-13 fold), but was greater in the GM1-treated groups (GM1 i.c.v., GM1 cap: 20-25 fold). In contrast, KCl-stimulated release of ACh in striata from GM1-treated lesioned groups was significantly less (5-10 fold), compared to the unlesioned controls (C: 16 fold) and lesioned vehicle-treated rats (V i.c.v. and V cap: 16-18 fold). The release of choline was not increased significantly by large concentrations of KCl present in the perfusion medium. In all experimental groups, and in both structures of the brain, ratios between stimulated and non-stimulated release of choline was between 0.7-1.2.(ABSTRACT TRUNCATED AT 250 WORDS)
Maysinger
D
D
Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada.
Herrera-Marschitz
M
M
Ungerstedt
U
U
Cuello
A C
AC
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000033:anatomy & histology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002794:Choline / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003956:Dialysis; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D005677:G(M1) Ganglioside; D002794:Choline; D000109:Acetylcholine