title: A decrease in brain catecholamines prevents oxiracetam antagonism of the effects of scopolamine on memory and brain acetylcholine.
abstract: The effect of oxiracetam on passive avoidance conditioned response and acetylcholine (ACh) levels in rats with selective lesions of the central monoaminergic pathways was investigated. The lesions were followed by a marked decrease in cortical serotonin (-88%), noradrenaline (-54%) and striatal dopamine (-57%) levels, while neither the performance of a passive avoidance conditioned response nor brain ACh levels were affected. Scopolamine (hyoscine) administration (0.63 mg/kg, s.c.) to lesioned rats exerted the expected amnesic effect, associated with a decrease in hippocampal, cortical and striatal ACh levels. In the rats with degeneration of dopaminergic and noradrenergic but not serotoninergic pathways, oxiracetam (50 and 100 mg/kg, s.c.) was unable to prevent both amnesia and the decrease in brain ACh levels caused by scopolamine. The effect of oxiracetam was prevented by haloperidol (0.2 mg/kg, s.c.). Our findings support the hypothesis that an interaction between monoaminergic and cholinergic neurotransmitter systems may be involved in the actions of nootropic drugs on cognitive functions.
authors.affiliation: Department of Preclinical and Clinical Pharmacology, University of Florence, Italy.
authors.forename: M G
authors.initials: MG
authors.lastname: Giovannini
authors.forename: G
authors.initials: G
authors.lastname: Spignoli
authors.forename: V
authors.initials: V
authors.lastname: Carlà
authors.forename: G
authors.initials: G
authors.lastname: Pepeu
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D003213:Conditioning, Psychological; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D008568:Memory / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism; D011619:Psychotropic Drugs / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012601:Scopolamine / Q000037:antagonists & inhibitors*; D012701:Serotonin / Q000378:metabolism; D013378:Substantia Nigra / Q000378:metabolism
chemical_list: D002395:Catecholamines; D011619:Psychotropic Drugs; D011759:Pyrrolidines; D012701:Serotonin; D012601:Scopolamine; D006220:Haloperidol; D000109:Acetylcholine; C040619:oxiracetam; D004298:Dopamine; D009638:Norepinephrine