Deficits in cholinergic neurotransmission markers induced by ethylcholine mustard aziridinium (AF64A) in the rat hippocampus: sensitivity to treatment with the monoamine oxidase-B inhibitor L-deprenyl

Drugs Exp Clin Res. 1992;18(5):163-71.

Abstract

Assessment was made of the effects of intracerebroventricular (i.c.v.) administration of ethylcholine mustard aziridinium (AF64A) and of the monoamine oxidase (MAO)-B inhibitor L-deprenyl on the acetylcholine (ACh) biosynthetic enzyme choline acetyltransferase (ChAT), on the ACh catabolic enzyme acetylcholinesterase (AChE) and on the density of ACh muscarinic M-1 and M-2 receptor sites. In addition, the effect of AF64A and of L-deprenyl treatment on the localization of AChE activity in the CA-1 and CA-3 fields of the hippocampus was evaluated by combined enzyme histochemistry and microdensitometry techniques. I.c.v. injection of AF64A induced, 4 weeks after administration of the neurotoxin, a remarkable increase of MAO-B activity, and a significant reduction of ChAT and AChE activities in the hippocampus but not in the neostriatum which was used as a reference tissue. Hippocampal muscarinic M-1 receptors were unaffected by AF64A administration, whereas M-2 sites were reduced after neurotoxin injection. Enzyme histochemistry analysis showed that the loss of AChE induced by AF64A was more pronounced in the CA-3 than in the CA-1 field of the hippocampus. Treatment with L-deprenyl induced, from a dose of 11.17 microM/kg/day, a significant reduction of MAO-B activity in the hippocampus. The expression of ChAT and AChE, as well as the density of M-2 receptors, was increased after L-deprenyl administration in the hippocampus but not in the neostriatum. An increase in AChE reactivity was noticeable in the CA-1 and CA-3 fields of the hippocampus of AF64A-injected rats treated with L-deprenyl.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / analysis*
  • Animals
  • Aziridines / administration & dosage
  • Aziridines / pharmacology*
  • Choline / administration & dosage
  • Choline / analogs & derivatives*
  • Choline / pharmacology
  • Choline O-Acetyltransferase / drug effects*
  • Hippocampus / chemistry*
  • Hippocampus / drug effects*
  • Hippocampus / pathology
  • Injections, Intraventricular
  • Male
  • Monoamine Oxidase Inhibitors / administration & dosage
  • Monoamine Oxidase Inhibitors / pharmacology*
  • Neostriatum / chemistry
  • Neostriatum / drug effects
  • Neostriatum / pathology
  • Neuromuscular Blocking Agents / administration & dosage
  • Neuromuscular Blocking Agents / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Muscarinic / analysis*
  • Selegiline / administration & dosage
  • Selegiline / pharmacology*
  • Toxins, Biological / administration & dosage
  • Toxins, Biological / pharmacology*

Substances

  • Aziridines
  • Monoamine Oxidase Inhibitors
  • Neuromuscular Blocking Agents
  • Receptors, Muscarinic
  • Toxins, Biological
  • Selegiline
  • ethylcholine aziridinium
  • Choline O-Acetyltransferase
  • Acetylcholinesterase
  • Choline