Increase in striatal acetylcholine by picrotoxin in the rat: evidence for a gabergic-dopaminergic-cholinergic link.
Picrotoxin, 2 mg/kg i.p., a GABA receptor blocking agent, increased rat striatal acetylcholine content by approximately 70% without altering the levels of this amine in the cerebral hemispheres, mesencephalon, diencephalon, hippocampus and cerebellum. Striatal choline levels were concomitantly decreased by about 25%. This dose of picrotoxin also increased striatal homovanillic acid levels by about 30%, an effect which was not antagonized by pretreatment with the dopamine receptor stimulating agent, piribedil. Picrotoxin did not affect striatal choline-O-acetyltransferase or cholinesterase activity after in vitro incubation. The action of picrotoxin on striatal acetylcholine levels was partially antagonized by pimozide and completely blocked by alpha-methyl-para-tyrosine pretreatment while the intraventricular injection of 6-hydroxydopamine was without effect. Convulsions were not prevented by any of these treatments. The results are interpreted as follows: picrotoxin released dopamine through disinhibition of the dopaminergic neurons as a result of blockade of gabergic receptors. The increased dopaminergic activity inhibited cholinergic neurons and lead to an increase in acetylcholine content. The data thus provide evidence for a possible gabergic (inhibitory)--dopaminergic (inhibitory)-cholinergic link terminating in the striatum.
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D002794:Choline / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002802:Cholinesterases / Q000378:metabolism; D003342:Corpus Striatum / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology; D004298:Dopamine / Q000502:physiology; D005260:Female; D006719:Homovanillic Acid / Q000378:metabolism; D006892:Hydroxydopamines / Q000494:pharmacology; D008781:Methyltyrosines / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology*; D010868:Pimozide / Q000494:pharmacology; D010891:Piribedil / Q000494:pharmacology; D051381:Rats; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D000109:Acetylcholine; D001205:Ascorbic Acid; D002794:Choline; D002795:Choline O-Acetyltransferase; D002802:Cholinesterases; D004298:Dopamine; D006719:Homovanillic Acid; D006892:Hydroxydopamines; D008781:Methyltyrosines; D010852:Picrotoxin; D010868:Pimozide; D010891:Piribedil; D005680:gamma-Aminobutyric Acid