The priming effect of rewarding brain stimulation in rats depends on both the cost and strength of reward but survives blockade of D2-like dopamine receptors.

Receipt of an intense reward boosts motivation to work for more of that reward. This phenomenon is called the priming effect of rewards. Using a novel measurement method, we show that the priming effect of rewarding electrical brain stimulation depends on the cost, as well as on the strength, of the anticipated reward.

Combined effects of the contraceptive hormones, ethinyl estradiol and levonorgestrel, on the use of place and response memory in gonadally-intact female rats.

During maze navigation rats can rely on hippocampus-mediated place memory or striatum-mediated response memory. Ovarian hormones bias whether females use place or response memory to reach a reward. Here, we investigated the impact of the contraceptive hormones, ethinyl estradiol (EE) and levonorgestrel (LNG), on memory bias.

The role of progesterone in memory bias during spatial navigation in females.

Rats can use several memory systems to navigate a maze toward a reward. Two of these are place memory and response memory and female rats can be biased to predominantly use one over another. Both progesterone and estrogens have been shown to alter memory bias.

Modeling hormonal contraception in female rats: A framework for studies in behavioral neurobiology.

Research on hormonal contraceptives (HC) in animal models is lacking, and as a result, so is our understanding of the impact of HC on the brain and behavior. Here, we provide a review of the pharmacology of HC, as well as the methodology and best practices for designing a model of HC in female rats. We outline specific methodological considerations regarding dosing, route of administration, exposure time/timing, and selecting a control group.

Estrogen receptors observed at extranuclear neuronal sites and in glia in the nucleus accumbens core and shell of the female rat: Evidence for localization to catecholaminergic and GABAergic neurons.

Estrogens affect dopamine-dependent diseases/behavior and have rapid effects on dopamine release and receptor availability in the nucleus accumbens (NAc). Low levels of nuclear estrogen receptor (ER) α and ERβ are seen in the NAc, which cannot account for the rapid effects of estrogens in this region. G-protein coupled ER 1 (GPER1) is observed at low levels in the NAc shell, which also likely does not account for the array of estrogens' effects in this region.

Progesterone rapidly alters the use of place and response memory during spatial navigation in female rats.

17β-Estradiol (E2) and progesterone (P) influence place and response memory in female rats in spatial navigation tasks. Use of these memory systems is associated with the hippocampus and the dorsal striatum, respectively. Injections of E2 result in a well-established bias to use place memory, while much less is understood about the role of P.

Fos expression is increased in oxytocin neurons of female rats with a sexually conditioned mate preference for an individual male rat.

Evidence suggests an important role of Pavlovian learning in sexual partner selection. Female rats that experience paced copulation with a male scented with a neutral odor selectively solicit and receive ejaculations from the scented male relative to an unscented male. Exposure to the conditioned odor alone induces Fos protein in regions of the brain associated with sexual excitation.

The priming effect of food persists following blockade of dopamine receptors.

The priming effect of rewards is a boost in the vigor of reward seeking resulting from the previous receipt of a reward. Extensive work has been carried out on the priming effect of electrical brain stimulation, but much less research exists on the priming effect of natural rewards, such as food. While both reinforcement and motivation are linked with dopamine transmission in the brain, the priming effect of rewards does not appear to be dopamine-dependent.

Varying the rate of intravenous cocaine infusion influences the temporal dynamics of both drug and dopamine concentrations in the striatum.

The faster drugs of abuse reach the brain, the greater is the risk of addiction. Even small differences in the rate of drug delivery can influence outcome. Infusing cocaine intravenously over 5 vs.

17β-estradiol locally increases phasic dopamine release in the dorsal striatum.

Studies using in vivo microdialysis have shown that 17β-estradiol (E2) increases dopamine (DA) transmission in the dorsal striatum. Both systemic administration of E2 and local infusion into the dorsal striatum rapidly enhance amphetamine-induced DA release. However, it is not known to what degree these effects reflect tonic and/or phasic DA release.

Interactions between estradiol and haloperidol on perseveration and reversal learning in amphetamine-sensitized female rats.

There are sex differences associated with schizophrenia, as women exhibit later onset of the disorder, less severe symptomatology, and better response to antipsychotic medications. Estrogens are thought to play a role in these sex differences; estrogens facilitate the effects of antipsychotic medications to reduce the positive symptoms of schizophrenia, but it remains unclear whether estrogens protect against the cognitive symptoms of this disorder. Amphetamine sensitization is used to model some symptoms of schizophrenia in rats, including cognitive deficits like excessive perseveration and slower reversal learning.

Intra-perirhinal cortex administration of estradiol, but not an ERβ agonist, modulates object-recognition memory in ovariectomized rats.

Intra-rhinal cortical infusion of 17-β estradiol (E2, 244.8pg/μl) enhances performance on the Novel-Object Preference (NOP) test and impairs accuracy on the delayed nonmatching-to-sample (DNMS) task in the same set of ovariectomized rats (Gervais, Jacob, Brake, & Mumby, 2013). These results appear paradoxical, as normal performance on both tests require intact object-recognition memory (ORM) ability.

17β-Estradiol infusions into the dorsal striatum rapidly increase dorsal striatal dopamine release in vivo.

Systemic injections of 17β-estradiol (E2) in ovariectomized (OVX) female rats rapidly enhance dorsal striatal dopamine (DA) release in response to amphetamine (AMPH). Additionally, a single injection of E2 rapidly (within 30min) enhances amphetamine-induced DA release. In situ studies show that this rapid effect of E2 occurs specifically within the dorsal striatum (DS).

Modulation of spatial and response strategies by phase of the menstrual cycle in women tested in a virtual navigation task.

Different memory systems are employed to navigate an environment. It has been consistently shown in rodents that estrogen impacts multiple memory system bias such that low estradiol (E2) is associated with increased use of a striatal-mediated response strategy whereas high E2 increases use of a hippocampal-dependent spatial memory. Low E2 also enhances performance on a response-based task whereas high E2 levels improve learning on a spatial task.

High estrogen and chronic haloperidol lead to greater amphetamine-induced BOLD activation in awake, amphetamine-sensitized female rats.

The ovarian hormone estrogen has been implicated in schizophrenia symptomatology. Low levels of estrogen are associated with an increase in symptom severity, while exogenous estrogen increases the efficacy of antipsychotic medication, pointing at a possible interaction between estrogen and the dopaminergic system. The aim of this study is to further investigate this interaction in an animal model of some aspects of schizophrenia using awake functional magnetic resonance imaging.

Estrogen receptor α and G-protein coupled estrogen receptor 1 are localized to GABAergic neurons in the dorsal striatum.

Estrogens affect dopamine transmission in the striatum, increasing dopamine availability, maintaining D2 receptor density, and reducing the availability of the dopamine transporter. Some of these effects of estrogens are rapid, suggesting that they are mediated by membrane associated receptors. Recently our group demonstrated that there is extra-nuclear labeling for ERα, ERβ, and GPER1 in the striatum, but that ERα and GPER1 are not localized to dopaminergic neurons in this region.

Ovarian steroids alter dopamine receptor populations in the medial preoptic area of female rats: implications for sexual motivation, desire, and behaviour.

Dopamine (DA) transmission in the medial preoptic area (mPOA) plays a critical role in the control of appetitive sexual behaviour in the female rat. We have shown previously that a DA D1 receptor (D1R)-mediated excitatory state appears to occur in females primed with estradiol benzoate (EB) and progesterone (P), whereas a DA D2 receptor (D2R)-mediated inhibitory state appears to occur in females primed only with EB. The present experiment employed three techniques to better understand what changes occur to DA receptors (DARs) in the mPOA under different hormonal profiles.

Estrogen receptors in the central nervous system and their implication for dopamine-dependent cognition in females.

This article is part of a Special Issue "Estradiol and cognition". Over the past 30 years, research has demonstrated that estrogens not only are important for female reproduction, but also play a role in a diverse array of cognitive functions. Originally, estrogens were thought to have only one receptor, localized exclusively to the cytoplasm and nucleus of cells.

Attenuation of dendritic spine density in the perirhinal cortex following 17β-Estradiol replacement in the rat.

Intraperirhinal cortex infusion of 17-β estradiol (E2) impairs object-recognition memory. However, it is not currently known whether this hormone modulates synaptic plasticity in this structure. Most excitatory synapses in the central nervous system are located on dendritic spines, and elevated E2 levels influence the density of these spines in several brain areas.

Changes in brain volume in response to estradiol levels, amphetamine sensitization and haloperidol treatment in awake female rats.

Estrogen has been shown to further ameliorate symptoms when administered in conjunction with antipsychotics in patients with schizophrenia. We have previously shown that chronic haloperidol (HAL) treatment reduces amphetamine (AMPH)-induced locomotor activity in AMPH-sensitized rats, but only when paired with high levels of the estrogen, 17-β estradiol. In addition, we reported estradiol-dependent responses to AMPH in AMPH-sensitized rats as measured by functional magnetic resonance imaging.

Integration of neural networks activated by amphetamine in females with different estrogen levels: a functional imaging study in awake rats.

Previous studies demonstrate that schizophrenia symptomatology in women is dependent upon estrogen levels. Estrogen has beneficial properties when administered in conjunction with antipsychotics, and estrogen also alters, in rats, dopamine neurotransmission, which is a common target of all antipsychotic medications, suggesting a possible interaction between the two. The aim of the current study was to investigate this possible interaction using functional magnetic resonance imaging in awake, female rats.

Medial prefrontal cortical estradiol rapidly alters memory system bias in female rats: ultrastructural analysis reveals membrane-associated estrogen receptors as potential mediators.

High plasma levels of estradiol (E2) are associated with use of a place memory system over a response memory system. We examined whether infusing estradiol into the medial prefrontal cortex (mPFC) or anterior cingulate cortex (AC) could affect memory system bias in female rats. We also examined the ultrastructural distribution of estrogen receptor (ER)-α, ERβ, and G protein-coupled estrogen receptor 1 (GPER1) in the mPFC of female rats as a mechanism for the behavioral effects of E2 in the mPFC.

Modulatory effect of 17-β estradiol on performance of ovariectomized rats on the Shock-Probe test.

17-β estradiol (E2) has been shown to modulate fear conditioning by influencing freezing behavior following re-exposure to either the conditioning context or a cue associated with shock. Fear-related behaviors other than freezing may be influenced differently by E2 replacement. Accordingly, the present study examined whether E2 modulates fear conditioning using the Shock-Probe test, which allows for the observation of multiple fear responses.

Estrogen potentiates the behavioral and nucleus accumbens dopamine response to continuous haloperidol treatment in female rats.

Estrogen has been shown to enhance the effects of antipsychotics in humans. To investigate the mechanisms of how this may occur, the current study examined estradiol's effects on dopaminergic transmission and behavior in amphetamine-sensitized and non-sensitized female rats. Sixty-four ovariectomized female Sprague-Dawley rats were used for this study.