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Post-ischemic administration of bifemelane hydrochloride prohibits ischemia-induced depletion of the muscarinic M1-receptor and its mRNA in the gerbil hippocampus

1992; Elsevier BV; Volume: 591; Issue: 1 Linguagem: Inglês

10.1016/0006-8993(92)90993-j

1872-6240

N Ogawa, Masato Asanuma, Kiminao Mizukawa, Hiromi Hirata, H. Chou, A. Mori,

Neuroscience and Neuropharmacology Research

Parallel determinations of muscarinic cholinergic M1 receptor (M1-R) binding and of M1-R mRNA levels were carried out in the gerbil hippocampus 14 days after 5 min of transient ischemia. Both were reduced in the ischemic tissue to about 50% of the levels found in sham-operated controls, indicating that the late loss of M1-R is probably decreased synthesis. Three administrations of bifemelane hydrochloride (15 mg/kg, i.p., just after ischemia and 6 and 12 h later) completely prevented neuronal death in the hippocampus and ischemia-induced losses of hippocampal M1-R and its mRNA. Since vascular dementia may depend upon the ischemia-induced losses in cholinergic communication in the hippocampus, these findings suggest that it may be possible to prevent its occurrence by post-ischemic treatment with bifemelane hydrochloride.