S. Glisson, A. Karczmar, L. Barnes
Jul 1, 1974
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Journal
Neuropharmacology
Abstract
Abstract Diisopropyl phosphorofluoridate (DFP) was administered to rabbits in which the pretreatment with a monoamine oxidase inhibitor, JB835, and DOPA caused an elevation in nore-pinephrine (NE) and, to a lesser extent, in dopamine (DA) levels in the thalamus, hypothalamus, midbrain and hippocampus. Pretreatment with JB835-DOPA combination and/or elevation of NE and of DA caused no significant effect upon either cholinesterase activity or acetylcholine (ACh) levels in the caudate nucleus, midbrain, thalamus or hypothalamus. Diisopropyl phosphorofluoridate caused nearly complete inhibition of cholinesterase activity in all these brain parts whether or not the animals were pretreated with JB835 and DOPA, and with atropine. Diisopropyl phosphorofluoridate induced elevation of levels of ACh was somewhat lowered by JB835-DOPA pretreatment in the case of the thalamus and hypothalamus but not in that of the caudate nucleus or midbrain; atropine but not atropine methyl nitrate further lowered ACh levels in all brain parts. Diisopropyl phosphorofluoridate caused a decrease of NE levels and elevation of DA levels in all 4 brain parts of the pretreated rabbits. In identically pretreated animals atropine methyl nitrate given prior to DFP prevented the DA increase but was without effect upon the NE decrease in these brain parts. Dopamine was affected maximally in the hypothalamus, midbrain and thalamus concomitantly with major increments in ACh at these sites. Maximal decreases in NE occurred in the caudate, thalamus and midbrain; the extent of these changes did not parallel that of the changes in ACh. These findings confirm our earlier results (Glisson, Karczmar and Barnes, 1972) and expand them to additional brain parts. They are discussed with respect to brain localization of ACh and catecholamine systems.