Behavioural neuroscienceEstrogen modulates learning in female rats by acting directly at distinct memory systems
Section snippets
Subjects
Three-month-old Sprague–Dawley virgin, female rats were obtained from Harlan (Oregon, WI, USA barrier) in squads of 10–12 rats. Rats were housed individually in plastic cages with free access to food and water until food restriction was initiated. Lights were maintained on a 12-h light/dark cycle. Rats were given at least one week to habituate to the vivarium before any procedures were initiated.
All rats underwent bilateral ovariectomy 21 days prior to behavioral training. They were allowed
Results
Rats included in the final analyses showed typical diestrous vaginal smears of ovariectomized rats for five days prior to training (data not shown), indicating a lack of estrous cycles.
Discussion
Our findings suggest that estrogen acts at distinct neural sites to modulate performance on two maze tasks that differ in the cognitive strategy required for successful completion. Specifically, hormone injections into the hippocampus but not striatum of ovariectomized rats enhanced place learning, a task requiring the use of extramaze cues to find a food reward. The enhancement following intrahippocampal estrogen treatment reflected a reversal of impairment caused by cannula implantation.
Conclusions
Our findings suggest that estrogen’s effects on place and response learning result from independent actions at the hippocampus and striatum, respectively. The enhancement of place learning is supported by a broad literature reporting many effects of estrogen on the neurochemistry and physiology of the hippocampal system. The neural mechanisms that underlie the impairment of response learning are less clear, but may relate to downstream consequences in the striatum of estrogen-induced modulation
Acknowledgments
Supported by NSF IBN 0081061, IOB 0520876, and NIH/HD07333.
References (88)
- et al.
Estrogen increases G protein coupled receptor kinase 2 in the cortex of female rats
Brain Res
(2001) - et al.
Sex differences in the rapid and acute effects of estrogen on striatal D2 dopamine receptor binding
Brain Res
(1994) Gender differences in dopaminergic function in striatum and nucleus accumbens
Pharmacol Biochem Behav
(1999)- et al.
The influence of estrogen on nigrostriatal dopamine activity: behavioral and neurochemical evidence for both pre- and postsynaptic components
Behav Brain Res
(1986) - et al.
Neuroanatomical bases of spatial memory
Brain Res
(1980) - et al.
Estradiol facilitates performance as working memory load increases
Psychoneuroendocrinology
(1999) - et al.
Intrahippocampal lidocaine injections impair acquisition of a place task and facilitate acquisition of a response task in rats
Behav Brain Res
(2003) - et al.
Caudate nucleus and memory for egocentric localizatin
Behav Neural Biol
(1988) - et al.
Estrogen facilitates induction of long term potentiation in the hippocampus of awake rats
Brain Res
(1997) - et al.
Evidence for the substantia nigra pars compacta as an essential component of a memory system independent of the hippocampal memory system
Neurobiol Learn Mem
(2003)
Estrogen enhances performance of female rats during acquisition of a radial arm maze
Horm Behav
Estrogen replacement in ovariectomized rats affects strategy selection in the Morris water maze
Neurobiol Learn Mem
Estrogen increases the sensitivity of ovariectomized rats to the disruptive effects produced by the antagonism of D2 but not D1 dopamine receptors during performance of a response learning task
Horm Behav
Ovariectomy-induced disruption of long-term synaptic depression in the hippocampal CA1 region in vivo is attenuated with chronic estrogen replacement
Neurobiol Learn Mem
Gonadal steroids, learning and memory
Steroid hormones affect limbic afterdischarge thresholds and kindling rates in adult female rats
Brain Res
Effect of estrogen on changes in the activity of striatal cholinergic neurons induced by DA drugs
Brain Res
Estrogen improves performance of reinforced T-maze alternation and prevents the amnestic effects of scopolamine administered systemically or intrahippocampally
Neurobiol Learn Mem
Estrogen improves working but not reference memory and prevents amnestic effects of scopolamine of a radial-arm maze
Pharmacol Biochem Behav
Regional effect of estradiol on rat caudate-putamen dopamine receptors: lateral-medial differences
Neurosci Lett
High levels of estradiol disrupt conditioned place preference learning, stimulus response learning and reference memory but have limited effects on working memory
Behav Brain Res
Estrogen replacement enhances acquisition of a spatial memory task and reduces deficits associated with hippocampal muscarinic receptor inhibition
Horm Behav
Long-term treatment with estrogen and progesterone enhances acquisition of a spatial memory task by ovariectomized aged rats
Neurobiol Aging
Effects of raloxifene and estradiol on hippocampal acetylcholine release and spatial learning in the rat
Psychoneuroendocrinology
Effects of estrogen on potassium-stimulated acetylcholine release in the hippocampus and overlying cortex of adult rats
Brain Res
Activities of estrogen receptor α- and β-selective ligands at diverse estrogen responsive gene sites mediating transactivation or transrepression
Mol Cell Endocrinol
The effect of steroid sulfatase inhibition on learning and spatial memory
Brain Res
Dissociation of the contributions of the prefrontal cortex and dorsomedial thalamic nucleus to spatially guided behavior in the rat
Behav Brain Res
Role of estrogen in balancing contributions from multiple memory systems
Neurobiol Learn Mem
Shifts in preferred learning strategy across the estrous cycle in female rats
Horm Behav
Estradiol increases choline acetyltransferase activity in specific basal forebrain nuclei and projection areas of female rats
Exp Neurol
Estradiol enhances learning and memory in a spatial memory task and effects levels of monoaminergic neurotransmitters
Horm Behav
Short-term estrogen treatment in ovariectomized rats augments hippocampal acetylcholine release during place learning
Neurobiol Learn Mem
Parallel information processing in the water maze: evidence for independent memory systems involving dorsal striatum and hippocampus
Behav Neural Biol
Impaired learning in a spatial working memory version and in a cued version of the water maze in rats with MPTP-induced mesencephalic dopaminergic lesions
Brain Res Bull
Parallel processing across neural systems: implications for a multiple memory system hypothesis
Neurobiol Learn Mem
Inactivation of hippocampus or caudate nucleus with lidocaine differentially affects expression of place and response learning
Neurobiol Learn Mem
Posttraining estradiol injections enhance memory in ovariectomized rats: cholinergic blockade and synergism
Neurobiol Learn Mem
Amygdala modulation of multiple memory systems: hippocampus and caudate-putamen
Neurobiol Learn Mem
Estradiol in the striatum: effects on behavior and dopamine receptors but no evidence for membrane steroid receptors
Brain Res Bull
Autonomic and cardiovascular reflex responses to central estrogen injection in ovariectomized female rats
Brain Res
Role of estrogen replacement therapy in memory enhancement and the prevention of neuronal loss associated with Alzheimer’s Disease
Am J Med
Ovarian steroid deprivation results in a reversible learning impairment and compromised cholinergic function in female Sprague-Dawley rats
Brain Res
Sex differences in the dynamics of cue utilization and exploratory behavior
Behav Brain Res
Cited by (130)
Beyond sex and gender differences: The case for women's health research
2023, Principles of Gender-Specific Medicine: Sex and Gender-Specific Biology in the Postgenomic EraHippocampus-sensitive and striatum-sensitive learning one month after morphine or cocaine exposure in male rats
2022, Pharmacology Biochemistry and BehaviorCitation Excerpt :A third set of rats was trained on a dual solution T-maze in which either place or response strategies afford effective solutions; probe tests administered after dual-solution training identify the dominant strategy used on the task (Restle, 1957; Tolman et al., 1946). These tasks have been used reliably to reveal changes across multiple memory system functions resulting from extensive training, advanced age, stress, and hormone status (e.g., Gardner et al., 2013, 2016, 2020a, 2020b; Gold et al., 2013; Gold, 2016; Hawley et al., 2012; Korol and Pisani, 2015; Korol and Wang, 2018; Packard and Goodman, 2012, 2013; Packard et al., 2018; Packard and McGaugh, 1996; Schwabe, 2013; Zurkovsky et al., 2007). Additional experiments measured tissue levels of glial fibrillary acidic protein (GFAP), brain-derived neurotrophic factor (BDNF), and glycogen synthase kinase-3 beta (GSK3β) across brain regions one month after cocaine or morphine exposure.
Time-dependent changes in hippocampal and striatal glycogen long after maze training in male rats
2021, Neurobiology of Learning and MemoryInfluence of ovarian hormones on value-based decision-making systems: Contribution to sexual dimorphisms in mental disorders
2021, Frontiers in NeuroendocrinologyCitation Excerpt :Reinforcement learning paradigms in animals have been based on appropriate responses (correct physical turn towards reward) and place learning (physical reward placement in the environment) for rewards and associated with brain structures, such as dorsal striatum for response learning and hippocampus for place learning (Shelton et al., 2013). Experiments with response learning in normally cycling and ovariectomized rats have demonstrated that direct administration of estradiol to the dorsal striatum impaired response learning (Davis et al., 2005; Zurkovsky et al., 2007; Wang et al., 2008). Combined with a D2-receptor antagonist but not D1-receptor antagonist, chronic estradiol treatment of ovariectomized rats resulted in increased response learning error rates (Daniel et al., 2006).
Dose-dependent effects of testosterone on spatial learning strategies and brain-derived neurotrophic factor in male rats
2020, Psychoneuroendocrinology