Muscarinic receptor plasticity in rats lesioned in the nucleus basalis of Meynert.
The present study investigated the effects of chronic treatment with scopolamine (10 mg/kg i.p. for 21 days) on the muscarinic acetylcholine receptors in the frontoparietal cortex of rats, lesioned at the level of the nucleus basalis of Meynert. Ibotenic acid (25 nmol in 0.5 microliters) was injected bilaterally or unilaterally into the area of this nucleus and produced a major impairment of the cortical cholinergic system. These lesions depleted specifically frontoparietal cortical choline acetyltransferase activity. Sham-operated rats were similarly operated but no neurotoxin was injected. The chronic treatment with scopolamine caused a significant increase in the binding of [3H](-)quinuclidinylbenzilate to muscarinic receptors in the frontoparietal cortex of control and sham-operated rats but not in lesioned animals. This increase was due to an up-regulation in the number of muscarinic acetylcholine receptors, without significant change in their affinity. These results suggest that a functional presynaptic cholinergic terminal is necessary for the plasticity of muscarinic receptors in the central nervous system.
Department of Biochemical Pharmacology Centre de Recherche Pierre Fabre, Castres, France.
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D000818:Animals; D001479:Basal Ganglia / Q000502:physiology*; D002540:Cerebral Cortex / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007051:Ibotenic Acid / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D011813:Quinuclidinyl Benzilate; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012601:Scopolamine / Q000494:pharmacology; D013377:Substantia Innominata / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*
D011976:Receptors, Muscarinic; D007051:Ibotenic Acid; D011813:Quinuclidinyl Benzilate; D012601:Scopolamine; D002795:Choline O-Acetyltransferase