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.
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)
Ricci
A
A
Department of Cardiovascular and Respiratory Sciences, University La Sapienza, Rome, Italy.
Mancini
M
M
Strocchi
P
P
Bongrani
S
S
Bronzetti
E
E
D000110:Acetylcholinesterase / Q000032:analysis*; D000818:Animals; D001388:Aziridines / Q000008:administration & dosage / Q000494:pharmacology*; D002794:Choline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D002795:Choline O-Acetyltransferase / Q000187:drug effects*; D006624:Hippocampus / Q000737:chemistry* / Q000187:drug effects* / Q000473:pathology; D007276:Injections, Intraventricular; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D017072:Neostriatum / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D009466:Neuromuscular Blocking Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000032:analysis*; D012642:Selegiline / Q000008:administration & dosage / Q000494:pharmacology*; D014118:Toxins, Biological / Q000008:administration & dosage / Q000494:pharmacology*
D001388:Aziridines; D008996:Monoamine Oxidase Inhibitors; D009466:Neuromuscular Blocking Agents; D011976:Receptors, Muscarinic; D014118:Toxins, Biological; D012642:Selegiline; C044894:ethylcholine aziridinium; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D002794:Choline