Action of a chronic disulfiram administration on memory decay and on central cholinergic and adrenergic systems.
The chronic administration (15 days) of disulfiram reduced the levels of noradrenaline (NA) in the olfactory system and in the subcortex at all the tested doses (50, 200 and 400 mg/kg/day). No modification of the density (Bmax) and of the dissociation constant (Kd) for alpha 1-adrenergic receptors was observed (radioligand [3H]prazosin). Only in the hippocampus the acetylcholine (ACh) levels and the Bmax for muscarinic receptors (radioligand [3H]QNB) were increased at all doses tested. Modifications of the cholinergic system were observed in the subcortex and in the cortex only at the higher doses of disulfiram. After 20 days interruption of the daily training in the staircase maze, 50, 100 and 200 mg/kg/day of disulfiram accelerated spontaneous decay of memory. It is hypothesized that the modifications of the hippocampal cholinergic system (increase of the ACh levels and of the density of the muscarinic receptors) may be the condition determining the acceleration of the decay of memory caused by disulfiram.
Molinengo
L
L
Istituto di Farmacologia e Farmacognosia, Università di Torino, Turin, Italy.
Oggero
L
L
Ghi
P
P
Orsetti
M
M
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003216:Conditioning, Operant / Q000187:drug effects; D004221:Disulfiram / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013997:Time Factors
D011942:Receptors, Adrenergic, alpha; D011976:Receptors, Muscarinic; D000109:Acetylcholine; D004221:Disulfiram; D009638:Norepinephrine