Estrogen levels modify scopolamine-induced amnesia in gonadally intact rats

• Published in: Progress in neuro-psychopharmacology & biological psychiatry Vol. 53; pp. 99 - 108
• Main Authors: de Macêdo Medeiros, André, Izídio, Geison Souza, Sousa, Diego Silveira, Macedo, Priscila Tavares, Silva, Anatildes Feitosa, Shiramizu, Victor Kenji Medeiros, Cabral, Alicia, Ribeiro, Alessandra Mussi, Silva, Regina Helena
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 04-08-2014; Elsevier
• Subjects: Adult and adolescent clinical studies; Amnesia - chemically induced; Amnesia - complications; Amnesia - metabolism; Analysis of Variance; Animals; Anxiety - etiology; Anxiety-like behavior; Avoidance Learning - drug effects; Biological and medical sciences; Cholinergic Antagonists - toxicity; Cholinergic transmission; Contraceptive Agents - pharmacology; Discriminative avoidance task; Disease Models, Animal; Disorders of higher nervous function. Focal brain diseases. Central vestibular syndrome and deafness. Brain stem syndromes; Estradiol - analogs & derivatives; Estradiol - pharmacology; Estrogens - metabolism; Estrous cycle; Estrous Cycle - drug effects; Female; Maze Learning - drug effects; Medical sciences; Memory; Motor Activity - drug effects; Nervous system (semeiology, syndromes); Neurology; Neuropharmacology; Organic mental disorders. Neuropsychology; Pharmacology. Drug treatments; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Rats; Rats, Wistar; Scopolamine Hydrobromide - toxicity; Time Factors; DIE; NO; NAV; Discriminative avoidance task; Memory; EST; TOA; TAV; Anxiety-like behavior; MW; RIA; PRO; ER; PMDAT; EV; OA; AV; VEH; WHI; Estrous cycle; MET; SCO; SAL; Cholinergic transmission; Memory disorder; Cognitive disorder; Rat; Estrogen; Alkaloid; Anxiety; Amnesia; Behavior; Neurological disorder; Hyoscine; Nervous system diseases; Rodentia; Ovarian hormone; Cerebral disorder; Anticholinergic agent; Vertebrata; Mammalia; Animal; Central nervous system disease; Sex steroid hormone; Avoidance
• ISSN: 0278-5846; 1878-4216
• DOI: 10.1016/j.pnpbp.2014.03.006

Previous studies suggested that estrogen plays a role in cognitive function by modulating the cholinergic transmission. However, most of the studies dealing with this subject have been conducted using ovariectomized rats. In the present study we evaluated the effects of physiological and supra-physiological variation of estrogen levels on scopolamine-induced amnesia in gonadally intact female rats. We used the plus-maze discriminative avoidance task (PMDAT) in order to evaluate anxiety levels and motor activity concomitantly to the memory performance. In experiment 1, female Wistar rats in each estrous cycle phase received scopolamine (1mg/kg) or saline i.p. 20min before the training session in the PMDAT. In experiment 2, rats in diestrus received estradiol valerate (1mg/kg) or sesame oil i.m., and scopolamine (1mg/kg) or saline i.p., 45min and 20min before the training, respectively. In experiment 3, rats in diestrus received scopolamine (1mg/kg) or saline i.p. 20min before the training, and estradiol valerate (1mg/kg) or sesame oil i.m. immediately after the training session. In all experiments, a test session was performed 24h later. The main results showed that: (1) scopolamine impaired retrieval and induced anxiolytic and hyperlocomotor effects in all experiments; (2) this cholinergic antagonist impaired acquisition only in animals in diestrus; (3) acute administration of estradiol valerate prevented the learning impairment induced by scopolamine and (4) interfered with memory consolidation process. The results suggest that endogenous variations in estrogen levels across the estrous cycle modulate some aspects of memory mediated by the cholinergic system. Indeed, specifically in diestrus, a stage with low estrogen levels, the impairment produced by scopolamine on the acquisition was counteracted by exogenous administration of the hormone, whereas the posttraining treatment potentiated the negative effects of scopolamine during the consolidation phase of memory.
•Scopolamine induced learning impairment specifically in diestrus.•Scopolamine-induced learning impairment was prevented by exogenous estradiol.•Posttraining estradiol potentiated the memory impairment induced by scopolamine.•A role of the cholinergic system is suggested for the estrogen mechanisms on memory.