The neurotoxic actions of ibotenic acid on cholinergic and opioid peptidergic systems in the central nervous system of the rat.
The neurotoxic effects produced by ibotenic acid (IA) induced chemical lesions of the central nervous system (CNS) cholinergic system were examined on the opioid peptidergic system in adult rats. Forebrain cholinergic systems were bilaterally lesioned by the infusion of IA (1 or 5 micrograms/site) into the nucleus basalis magnocellularis (NBM). One week after the injections, the animals were sacrificed, and activities of acetylcholinesterase (AChE), choline acetyltransferase (ChAT) and concentrations of beta-endorphin (beta-End) and Met-enkephalin (Met-Enk) were measured in different brain regions. Animals treated with IA showed a decrease in the activity of ChAT (-24%), AChE (-36%) and beta-End level (-33%) in the frontoparietal cortex (FC). For the first time we report that these changes were associated with a compensatory increase in the activity of ChAT (+27%), AChE (+25%), beta-End level (+66%) in the remaining part of the cortex, i.e. cortex devoid of frontal cortex (C-FC). Met-enkephalin level increased by 59% in the frontoparietal cortex and did not change in the cortex devoid of frontal cortex upon IA treatment. These results suggest that IA treatment results in changes in the activity of cortical ChAT and AChE, and beta-End level in the same direction. Injection of IA in the NBM did not cause a change in the activity of ChAT or AChE in other brain regions such as hippocampus, striatum or midbrain. In addition to cortex devoid of frontal cortex, midbrain also showed a significant increase in the beta-End level in the IA treated animals. However, pituitary beta-End decreased in the neurotoxin treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Rattan
A K
AK
Department of Pharmacology, Ohio State University, College of Medicine, Columbus 43210-1239.
Tejwani
G A
GA
D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D004744:Enkephalin, Methionine / Q000378:metabolism*; D007839:Functional Laterality; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007051:Ibotenic Acid / Q000008:administration & dosage / Q000633:toxicity*; D007263:Infusions, Parenteral; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009498:Neurotoxins / Q000008:administration & dosage / Q000633:toxicity*; D009928:Organ Specificity; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D001615:beta-Endorphin / Q000378:metabolism*
D009498:Neurotoxins; D007051:Ibotenic Acid; D004744:Enkephalin, Methionine; D001615:beta-Endorphin; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase