Nucleus basalis magnocellularis lesions: lack of biochemical and immunocytochemical recovery and effect of cholinesterase inhibitors on passive avoidance.
Lesions of the rat nucleus basalis magnocellularis (nBM) result in a marked decrease in cortical choline acetyltransferase (CAT) and in behavioral deficits. After unilateral ibotenic acid (IBO) lesions of the nBM in rats, there was a significant ipsilateral loss of frontal and parietal CAT, which did not recover for 3 months following surgery and was accompanied by a loss of CAT immunoreactivity in the peripallidal region. Bilateral ibotenate nBM lesions resulted in a marked deficit of one-trial step-through passive avoidance (PA) at 24 hours. Cholinesterase inhibitors including physostigmine, N-ethylaklylphenyl carbamate (RA-6), and N,N-methylethylphenyl carbamate (RA-7) were administered in separate experiments, for 2 days before retrieval testing or for 3 consecutive days during consolidation immediately following training. Nonsignificant improvements in PA latency were produced using 0.32 mg/kg physostigmine and 2.5 mg/kg RA-6 administered before retrieval testing. The results suggest that destruction of cholinergic neurons in the nBM are involved in the PA deficit, but does not exclude the possibility that damage to other neuronal systems may contribute to the observed behavioral deficit.
Thal
L J
LJ
Neurology Service, San Diego Veterans Administration Medical Center, California 92161.
Dokla
C P
CP
Armstrong
D M
DM
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001479:Basal Ganglia / Q000187:drug effects*; D001931:Brain Mapping; D002219:Carbamates / Q000494:pharmacology; D002795:Choline O-Acetyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D007051:Ibotenic Acid / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D048448:Phenylcarbamates; D010830:Physostigmine / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D013377:Substantia Innominata / Q000187:drug effects*; D014520:Urethane / Q000031:analogs & derivatives / Q000494:pharmacology
D002219:Carbamates; D002800:Cholinesterase Inhibitors; D048448:Phenylcarbamates; C058422:N,N-methylethylphenylcarbamate; D007051:Ibotenic Acid; D014520:Urethane; D010830:Physostigmine; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase