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Abstract

Regional differences in ethylcholine mustard aziridinium ion (AF64A)-induced deficits in presynaptic cholinergic markers for the rat central nervous system.

T W Vickroy, M Watson, S M Leventer, W R Roeske, I Hanin and H I Yamamura
Journal of Pharmacology and Experimental Therapeutics December 1985, 235 (3) 577-582;
T W Vickroy
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M Watson
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S M Leventer
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W R Roeske
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I Hanin
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H I Yamamura
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Abstract

Several highly selective biochemical markers were used to assess the persistent central cholinergic dysfunction which accompanies administration of the cholinergic neurotoxin ethylcholine mustard aziridinium ion (AF64A). Rats received a single bilateral intracerebroventricular injection of AF64A (3 nmol/3 microliter/side) or vehicle and measurements were carried out in the cerebral cortices, hippocampi and corpora striata at 7 and 21 days postinjection. The drug binding sites of muscarinic cholinergic receptors, as revealed by high-affinity binding of (-)-[3H]quinuclidinyl benzilate (a classical muscarinic antagonist), [3H]pirenzepine (a selective antagonist of the putative M1 muscarinic receptor subclass) and (+)-[3H]cis-methyldioxolane (a potent muscarinic agonist), were not significantly affected by AF64A treatment. As reported previously, activity of the cholinergic synthetic enzyme choline acetyltransferase was reduced markedly (60-65%) in the hippocampi of AF64A-treated rats. A similar reduction was noted in high-affinity binding of [3H]hemicholinium-3 (a putative radioligand for sodium-dependent high-affinity choline uptake sites on cholinergic nerve terminals) in hippocampal membranes (59-65%). However, in the cerebral cortex, these presynaptic cholinergic markers were differentially altered by AF64A pretreatment (choline acetyltransferase, unchanged; [3H]hemicholinium-3 binding, reduced by 59-65%). These results indicate that a single intracerebroventricular injection of AF64A promotes biochemical and possibly functional deficits in presynaptic cholinergic nerve terminals distal from the injection site while having minimal influences upon muscarinic cholinergic receptor populations.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 235, Issue 3
1 Dec 1985
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Abstract

Regional differences in ethylcholine mustard aziridinium ion (AF64A)-induced deficits in presynaptic cholinergic markers for the rat central nervous system.

T W Vickroy, M Watson, S M Leventer, W R Roeske, I Hanin and H I Yamamura
Journal of Pharmacology and Experimental Therapeutics December 1, 1985, 235 (3) 577-582;

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Abstract

Regional differences in ethylcholine mustard aziridinium ion (AF64A)-induced deficits in presynaptic cholinergic markers for the rat central nervous system.

T W Vickroy, M Watson, S M Leventer, W R Roeske, I Hanin and H I Yamamura
Journal of Pharmacology and Experimental Therapeutics December 1, 1985, 235 (3) 577-582;
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