Estrogen improves working but not reference memory and prevents amnestic effects of scopolamine of a radial-arm maze.

This study investigated the effect of estrogen treatment on working memory and reference memory of female rats. In addition, the impact of estrogen on the sensitivity of these two types of memory to the cholinergic antagonist scopolamine was investigated. At 35 days of ages, rats were ovariectomized and implanted chronically with Silastic capsules containing either 25% crystalline estradiol or 100% cholesterol. Thirty days after surgery, animals were trained on an eight-arm radial maze with four arms baited to assess both working and reference memory performance. Following training, females were given scopolamine hydrobromide (0.2 mg/kg i.p.) prior to retesting on the task. Results indicated that estrogen treatment improved working memory performance during maze acquisition but did not affect reference memory performance. Scopolamine treatment impaired performance on the working memory component, but not the reference memory component, while estrogen prevented the impairment of working memory by scopolamine. Results support previous evidence that estrogen selectively enhances performance on tasks that depend on working memory.

Estrogen improves performance of reinforced T-maze alternation and prevents the amnestic effects of scopolamine administered systemically or intrahippocampally.

In a previous study, administration of high doses of estradiol benzoate (100 microgram/kg for 3 days im) to ovariectomized Long-Evans rats counteracted impairments of reinforced T-maze alternation induced by systemic administration of scopolamine, a muscarinic receptor blocker. In the current study, daily administration of lower doses of estradiol benzoate (5 microgram/kg for 3 weeks sc) increased the number of correct reinforced alternations during T-maze acquisition in ovariectomized rats compared to oil-treated controls and prevented impairments of reinforced alternation induced by injection of scopolamine hydrobromide (0.2 mg/kg ip). Furthermore, scopolamine (20 microgram) delivered bilaterally to the dorsal hippocampus reduced reinforced T-maze alternation in ovariectomized rats previously trained to complete this task while daily treatment with estradiol benzoate (5 microgram/kg sc) for 1 week prior to scopolamine infusion counteracted this impairment. In summary, physiological levels of estrogen improved performance during acquisition of reinforced T-maze alternation and prevented impairments induced by scopolamine administered systemically or intrahippocampally.

Sexual behavior of Flinders Line female rats bred for differential cholinergic sensitivities.

Flinders Lines are two strains of rats selectively bred for their divergent physiological responses to cholinergic drug challenges. Flinders Sensitive Line (FSL) rats are highly sensitive to cholinergic stimulation of various autonomic and behavioral responses compared to Flinders Resistant Line (FRL) rats. Because cholinergic innervation contributes to the regulation of female sexual behaviors in rats, a study was conducted to compare the sexual responses of FSL females to those of FRL females, as well as to those of Long-Evans (LE) females, a conventional rat strain. Ovariectomized FSL rats exhibited significantly higher incidences of lordosis and proceptive behaviors than ovariectomized FRL and LE rats over a range of estrogen doses (2, 3, 4, 5, or 20 microgram(s)/kg estradiol benzoate at 48 h before testing) administered in combination with progesterone (1 or 2 mg/kg at 4-6 h before testing). In addition, the muscarinic antagonist scopolamine inhibited lordosis behavior strongly in FRL females over a range of doses (0.25, 0.5, 1, 2, or 4 mg/kg), but failed to inhibit lordosis in FSL females. Results indicate that FSL females are highly sensitive to the behavioral effects of gonadal steroids and highly insensitive to the effects of a muscarinic antagonist. The enhanced sexual behavioral responses of FSL females could be a consequence of their well-established cholinergic hypersensitivity or a consequence of other undocumented characteristics of FSL females such as hypersensitivity to ovarian hormones. FSL females could provide a valuable model for the study of estrogen action at behavioral, cellular, and molecular levels.

Estrogen enhances performance of female rats during acquisition of a radial arm maze.

Estrogen can influence the expression of behaviors not associated directly with reproduction, including learning and memory. However, the effects of estrogen on learning and memory in mammals are complex, dependent on a variety of factors. The radial arm maze is a traditional experimental task that takes advantage of the natural foraging strategy of rats and provides an appropriate measure for studying the effects of estrogen on working memory in this species. In the experiments reported here, ovariectomized rats were implanted subcutaneously with 5-mm Silastic capsules containing 25% estradiol diluted with cholesterol. Control females received 5-mm Silastic capsules containing 100% cholesterol. Results of three separate experiments demonstrated that estradiol administered by Silastic implants for 30 days prior to eight-arm radial maze training, during the 24 days of maze training, or both significantly improved working memory performance compared to females treated with cholesterol alone, as indicated by improved arm choice accuracy over trials. The positive effect of estradiol exposure prior to training suggests that estrogen may induce neuronal changes that persist beyond the period of exposure with functional consequences for behavior.

Estrogen and estrogen-progesterone treatments counteract the effect of scopolamine on reinforced T-maze alternation in female rats.

The purpose of the experiments was to determine if steroid hormone treatments would attenuate the effect of the muscarinic receptor blocker scopolamine on a memory task. Ovariectomized rats were trained first to alternate for food reward between the arms of a T maze. Following training, females treated with scopolamine hydrobromide (0.2 mg/kg ip) did not alternate correctly between the arms of the T maze and responded at chance levels. However, when estradiol benzoate (25 micrograms) was administered 72, 48, and 24 hr before testing alone or in combination with progesterone (500 micrograms) administered 4-6 hr before testing, females alternated successfully between the arms of the T maze following scopolamine administration. Results indicate that gonadal steroids can completely counteract the impairment of T maze performance induced by scopolamine in female rats.

Effects of a muscarinic antagonist on various components of female sexual behavior in the rat.

The effects of the muscarinic antagonist scopolamine on lordosis, solicitation, pacing, approach, attractivity, and activity were evaluated in ovariectomized rats brought into sexual receptivity with estrogen and progesterone. Systemic (1 mg/rat) or intraventricular (10 micrograms bilaterally) administration of scopolamine significantly reduced the incidence of lordosis and solicitation behaviors and disrupted typical pacing of sexual contacts with a stimulus male. In addition, females avoided contact with a stimulus male, but not a stimulus female, following intraventricular infusion of scopolamine. The levels of general activity and frequencies of sexual contacts were similar in females treated intraventricularly with scopolamine and vehicle solutions. Consequently, scopolamine disrupted various components of sexual behavior, including lordosis, solicitation, pacing, and approach, without altering female attractivity or general activity.