Learning In Male Rats Research Articles

State- and Circuit-Dependent Opponent Processing of Fear.

The presence of valence coding neurons in the basolateral amygdala (BLA) that form distinct projections to other brain regions implies functional opposition between aversion and reward during learning. However, evidence for opponent interactions in fear learning is sparse and may only be apparent under certain conditions. Here we test this possibility by studying the roles of the BLA→central amygdala (CeA) and BLA→nucleus accumbens (Acb) pathways in fear learning in male rats. First, we assessed the organization of these pathways in the rat brain. BLA→CeA and BLA→Acb pathways were largely segregated in the BLA but shared overlapping molecular profiles. Then we assessed activity of the BLA→CeA and BLA→Acb pathways during two different forms of fear learning-fear learning in a neutral context and fear learning in a reward context. BLA→CeA neurons were robustly recruited by footshock regardless of where fear learning occurred, whereas recruitment of BLA→Acb neurons was state-dependent because footshock only recruited this pathway in a reward context. Finally, we assessed the causal roles of activity in these pathways in fear learning. Photoinhibition of the BLA→CeA pathway during the footshock US impaired fear learning, regardless of where fear learning occurred. In contrast, photoinhibition of the BLA→Acb pathway augmented fear learning, but only in the reward context. Taken together, our findings show circuit- and state-dependent opponent processing of fear. Footshock activity in the BLA→Acb pathway limits how much fear is learned.

Enhancement of response learning in male rats with intrastriatal infusions of a BDNF - TrkB agonist, 7,8-dihydroxyflavone.

Enhancement of learning and memory by cognitive and physical exercise may be mediated by brain-derived neurotrophic factor (BDNF) acting at tropomyosin receptor kinase B (TrkB). Upregulation of BDNF and systemic administration of a TrkB agonist, 7,8-dihydroxyflavone (7,8-DHF), enhance learning of several hippocampus-sensitive tasks in rodents. Although BDNF and 7,8-DHF enhance functions of other brain areas too, these effects have mainly targeted non-cognitive functions. One goal of the present study was to determine whether 7,8-DHF would act beyond the hippocampus to enhance cognitive functions sensitive to manipulations of the striatum. Here, we examined the effects of intrastriatal infusions of 7,8-DHF on learning a striatum-sensitive response maze and on phosphorylation of TrkB receptors in 3-month-old male Sprague Dawley rats. Most prior studies of BDNF and 7,8-DHF effects on learning and memory have administered the drugs for days to months before assessing effects on cognition. A second goal of the present study was to determine whether a single drug treatment near the time of training would effectively enhance learning. Moreover, 7,8-DHF is often tested for its ability to reverse impairments in learning and memory rather than to enhance these functions in the absence of impairments. Thus, a third goal of this experiment was to evaluate the efficacy of 7,8-DHF in enhancing learning in unimpaired rats. In untrained rats, intrastriatal infusions of 7,8-DHF resulted in phosphorylation of TrkB receptors, suggesting that 7,8-DHF acted as a TrkB agonist and BDNF mimic. The findings that a single, intra-striatal infusion of 7,8-DHF 20 min before training enhanced response learning in rats suggest that, in addition to its trophic effects, BDNF modulates learning and memory through receptor mediated cell signaling events.

Saccharin aversion learning in male and female laboratory rats

The three experiments reported in the present research demonstrated that male rats acquire stronger saccharin aversion than females. Experiment 1 revealed that male rats were better than females in a single-trial saccharin aversion learning with a lithium chloride injection as the unconditioned stimulus (US), when normalizing saccharin intake data. Experiment 2 replicated this finding. The stronger saccharin aversion learning in male rats was also observed in Experiment 3 with wheel running as the US, assessed by the saccharin-vs.-water choice test conducted after six saccharin-running pairing days. Experiments 2 and 3 also showed that the magnitude of induced nausea, reflected in the kaolin clay ingestion, is equivalent between the sexes. Experiment 4 excluded the possibility that the observed sex difference in saccharin aversion is due to the sex difference in inherent saccharin preference. These results, taken together, suggest that potential factors of the sex difference in rats' conditioned taste aversion could include sex disparities in taste perception, the ability to associate taste with nausea, and/or the expression of association learning.

The Granular Retrosplenial Cortex Is Necessary in Male Rats for Object-Location Associative Learning and Memory, But Not Spatial Working Memory or Visual Discrimination and Reversal, in the Touchscreen Operant Chamber.

The retrosplenial cortex (RSC) is a hub of diverse afferent and efferent projections thought to be involved in associative learning. RSC shows early pathology in mild cognitive impairment and Alzheimer's disease (AD), which impairs associative learning. To understand and develop therapies for diseases such as AD, animal models are essential. Given the importance of human RSC in object-location associative learning and the success of object-location associative paradigms in human studies and in the clinic, it would be of considerable value to establish a translational model of object-location learning for the rodent. For this reason, we sought to test the role of RSC in object-location learning in male rats using the object-location paired-associates learning (PAL) touchscreen task. First, increased cFos immunoreactivity was observed in granular RSC following PAL training when compared with extended pretraining controls. Following this, RSC lesions following PAL acquisition were used to explore the necessity of the RSC in object-location associative learning and memory and two tasks involving only one modality: trial-unique nonmatching-to-location for spatial working memory and pairwise visual discrimination/reversal. RSC lesions impaired both memory for learned paired-associates and learning of new object-location associations but did not affect performance in either the spatial or visual single-modality tasks. These findings provide evidence that RSC is necessary for object-location learning and less so for learning and memory involving the individual modalities therein.

A history of avoidance does not impact extinction learning in male rats

Pervasive avoidance is one of the central symptoms of all anxiety-related disorders. In treatment, avoidance behaviors are typically discouraged because they are assumed to maintain anxiety. Yet, it is not clear if engaging in avoidance is always detrimental. In this study, we used a platform-mediated avoidance task to investigate the influence of avoidance history on extinction learning in male rats. Our results show that having the opportunity to avoid during fear acquisition training does not significantly influence the extinction of auditory-cued fear in rats subjected to this platform-mediated avoidance procedure, which constitutes a realistic approach/avoidance conflict. This holds true irrespective of whether or not avoidance was possible during the extinction phase. This suggests that imposing a realistic cost on avoidance behavior prevents the adverse effects that avoidance has been claimed to have on extinction. However, avoidance does not appear to have clear positive effects on extinction learning nor on retention either.

Prepubertal methylphenidate leads to sex-dependent differences in probabilistic discounting

Prescription psychostimulants, such as methylphenidate (MPH), have served as a first line treatment for ADHD and associated developmental disorders since 1961. Psychostimulants has been shown to improve attention, response inhibition, and reduce hyperactivity in patients with ADHD, as well as in non-clinical human populations and animals. While there is a considerable amount of preclinical research investigating the effects of stimulant medications on reward sensitivity and basic learning in male rats, less is understood about their effects in females. Further, there are competing theories on the long-term cognitive impact of MPH, specifically in children who do not have ADHD. To this end, Long-Evans female and male rats were exposed to methylphenidate (0, 2.5, 5 mg/kg, BID, IP) for 20 days during early development (PD10–29). After discontinuation of MPH into adulthood, rats (beginning PD 60) were trained and tested for risk-preference using a 2-choice probabilistic discounting task. For this task, rats were given an option between a ‘large-risky’ choice (3 sugar pellets delivered on a probabilistic VR schedule) and ‘small-certain’ choice (1 sugar pellet delivered on a FR schedule). Rats were subsequently tested on an open field conflict test. The results demonstrate that prepubertal exposure to MPH can have lasting effects on decision-making. Specifically, female rats treated with 2.5 mg/kg MPH displayed a decrease in preference for the risky option, whereas male rats treated with the same dose showed an overall increase in preference compared to sex-matched controls. Irrespective of sex, rats treated with 2.5 mg/kg MPH also demonstrated a decrease in anxiety/inhibitory behavior on the modified open field test compared to controls. These results were not due to differences in locomotor behavior. Overall, the study contributes to the growing body of evidence to suggest that MPH exposure early in development can have a sex-dependent impact on decision-making in adulthood.

Inhibition of androgenic pathway impairs encoding of cerebellar-dependent motor learning in male rats.

Cerebellar-dependent learning is essential for the adaptation of motor and no motor behaviors to changing contexts, and neuroactive steroids-mainly referred to as estrogens-may regulate this process. However, the role of androgens in this process has not been established, although they may affect cerebellar physiology. Thus, this study aims to determine whether the activation of androgenic neural pathways may take part in controlling the vestibuloocular (VOR) and optokinetic reflexes (OKR), which depend on a defined cerebellar circuitry. To answer this question, we acutely blocked the activation of androgen receptors (Ars) using systemic administration of the Ars antagonist flutamide (FLUT; 20mg/Kg) in peripubertal male rats. Then, we evaluated the FLUT effect on general oculomotor performance in the VOR and OKR as well as VOR adaptive gain increases and decreases. We used a paradigm causing fast VOR adaptation that combined in phase/out phase visuo-vestibular stimulations. We found that FLUT impaired the gain increase and decrease in VOR adaptation. However, FLUT altered neither acute nor overtime basal ocular-motor performance in the VOR or OKR. These findings indicate that the activation of androgenic neural pathways participates in phenomena leading to fast VOR adaptation, probably through the modulation of plasticity mechanisms that underlie adaptation of this reflex. Conversely, androgens may not be essential for neural information processing demands in basal ocular-motor reflexes. Moreover, our results suggest that androgens, possibly testosterone and dihydrotestosterone, could rapidly regulate motor memory encoding in the VOR adaptation, acting at both cerebellar and extracerebellar plasticity sites.

Alcohol Consumption during Adulthood Does Not Impair Later Go/No-Go Reversal Learning in Male Rats

Reversal learning tasks are used to model flexible decision-making in laboratory animals, and exposure to drugs of abuse can cause long-term impairments in reversal learning. However, the long-term effects of alcohol on reversal learning have varied. We evaluated whether six weeks of voluntary alcohol consumption through chronic intermittent alcohol access (elevated by food restriction) in adult male rats would impair rats in a go/no-go reversal learning task when tested at an interval beyond acute withdrawal. In our go/no-go task, rats were reinforced for pressing one lever or withholding from pressing another lever, and the identities of the two levers were switched twice (once rats reached an accuracy criterion). We found no evidence that prior alcohol consumption altered discrimination or reversal learning in our task. This replicates previous patterns from our laboratory that higher alcohol consumption in food-restricted rats did not impair discrimination or reversal learning in a different go/no-go task and that alcohol consumption in free-fed adolescent/early adult rats did not impair go/no-go discrimination or reversal learning in the same task. It is unclear whether this represents an insensitivity of this task to alcohol exposure generally or whether an alcohol exposure procedure that leads to higher blood ethanol concentration (BEC) levels would impair learning. More research is needed to investigate these possibilities.

Hippocampal BDNF regulates a shift from flexible, goal-directed to habit memory system function following cocaine abstinence.

ABSTRACTThe transition from recreational drug use to addiction involves pathological learning processes that support a persistent shift from flexible, goal‐directed to habit behavioral control. Here, we examined the molecular mechanisms supporting altered function in hippocampal (HPC) and dorsolateral striatum (DLS) memory systems following abstinence from repeated cocaine. After 3 weeks of cocaine abstinence (experimenter‐ or self‐administered), we tested new behavioral learning in male rats using a dual‐solution maze task, which provides an unbiased approach to assess HPC‐ versus DLS‐dependent learning strategies. Dorsal hippocampus (dHPC) and DLS brain tissues were collected after memory testing to identify transcriptional adaptations associated with cocaine‐induced shifts in behavioral learning. Our results demonstrate that following prolonged cocaine abstinence rats show a bias toward the use of an inflexible, habit memory system (DLS) in lieu of a more flexible, easily updated memory system involving the HPC. This memory system bias was associated with upregulation and downregulation of brain‐derived neurotrophic factor (BDNF) gene expression and transcriptionally permissive histone acetylation (acetylated histone H3, AcH3) in the DLS and dHPC, respectively. Using viral‐mediated gene transfer, we overexpressed BDNF in the dHPC during cocaine abstinence and new maze learning. This manipulation restored HPC‐dependent behavioral control. These findings provide a system‐level understanding of altered plasticity and behavioral learning following cocaine abstinence and inform mechanisms mediating the organization of learning and memory more broadly.

Dissociable involvement of estrogen receptors in perirhinal cortex-mediated object-place memory in male rats

Estrogens and the estrogen receptors (ER) - ERα, ERβ, and the G-protein coupled estrogen receptor (GPER) - are implicated in various forms of hippocampus (HPC)-dependent memory. However, the involvement of ER-related mechanisms in perirhinal cortex (PRh), which is necessary for object memory, remains much less clear. Moreover, there is a paucity of data assessing ER contributions to cognition in males,despite documented sex differences at the cellular level.We hypothesized that estrogens in PRh are important for object memory in males, assessingthe role of 17-βestradiol (E2), ERα, ERβ, GPER, and their downstream signaling pathways, in PRh-mediated object-in-place (OiP) memory in gonadally-intact male rats. Intra-PRh administration of E2 enhanced both long-term memory (LTM; 24 h) and short-term memory (STM; 20 min). Conversely, aromatase inhibition with letrozole impaired LTM and STM. The semi-selective ER inhibitor ICI 182780 impaired LTM, but not STM. This effect may be due to inhibition of ERβ, as the ERβagonist DPN, but not ERαagonist PPT, enhanced LTM. GPER was also found to be necessary in PRh, as the antagonist G15 impaired both LTM and STM. Western blot analyses demonstrated that phosphorylation levels of the extracellular signal-related kinase (ERK2 isoform), awell-establisheddownstream signaling pathway activated by estrogens through ERα/ERβ, was elevated in PRh 5 min following OiP learning.We also reportincreased levels of c-Jun N-terminal kinase (JNK; p46 and p54 isoforms) phosphorylation in PRh 5 min following learning,consistent with recent research linking GPER activation and JNK signaling in the HPC. This effect was abolished by intra-PRh administration of G15, but not letrozole, suggesting that JNK signaling is triggered via GPER activation during OiP learning, and is possibly E2-independent, similar to findings in the HPC. These results, therefore, reveal interesting dissociations between the roles of various ERs, possibly involving both estrogen-dependent and independent mechanisms, in PRh-mediated object-place learning in male rats.

Social Value Unblocks Pavlovian Reinforcement Learning in Male Rats

Many species, including humans, are sensitive to social signals and the valuation of these social cues is important in maintaining social interactions. Social value, derived from social cues, thus could act as a reinforcer and influence reward learning. Here, we introduce a novel task in rats that investigates if social value can drive reinforcement learning about novel stimuli. Using the blocking/unblocking paradigm originally developed in the (non-social) reinforcement learning literature, we found that when actor rats have fully learned a stimulus-reward association producing reward for themselves, adding a cue that predicted an additional reward delivery to a partner rat unblocked associative learning about this cue in the actor rats. In contrast, additional cues that did not predict additional reward remained blocked from acquiring associative value. In a control experiment where putative social cue exchange between the partnered rats was prevented, the normally unblocked cues now remained blocked as expected. Taken together, these results suggest that social value can drive reinforcement learning in rats, and that the transmission of social cues is necessary for this learning, driven by social value, to occur.

Changes in multiunit activity pattern in cerebellar cortex associated to olfactory cues during sexual learning in male rats

The cerebellum is a structure of the central nervous system which has been previously studied with different techniques and animal models and even humans, so it is associated with multiple functions such as cognition, memory, emotional processing, balance, control of movement, among others. Its relationship with sensory systems has already been explored, however, the role it plays in olfactory processing in the cerebellum is unclear. Several hypotheses have been proposed from work done in humans and animal models with neuroimaging and immunohistochemical techniques. Everything seems to indicate that the cerebellar function is of vital importance for the olfactory perception, being able to be controlling not only the olfactory aspect, but also the olfactory processing. In this study we analyzed the multiunit activity in the granular layer of the cerebellar vermis during olfactory stimulation: a session being sexually naive and during four sessions of sexual behavior learning. The amplitude was compared between male naive and sexual experts, as well as between olfactory stimuli. The amplitude of the sexually experienced rats showed the highest values compared to naive ones. Odor of receptive female causes the greatest amplitudes, however, in the control group the amplitude increased when they were sexually experts. The motor, sensory and associative learning generated by the acquisition of sexual experience modifies the activation pattern in the cerebellum by presenting neutral odors or associated with a reward.

Olfactory stimulation induces cerebellar vermis activation during sexual learning in male rats

The cerebellum is a complex structure mainly recognized for its participation in motor activity and balance, and less understood for its role in olfactory processing. Herein, we assessed Fos immunoreactivity (Fos-IR) in the cerebellar vermis following exposure to different odors during sexual training in male rats. Males were allowed to copulate for either one, three or five sessions. One day after the corresponding session they were exposed during 60 min to woodshaving that was either: clean (Control), sprayed with almond scent (Alm) or from cages of sexually receptive females (RF). The vermis of the cerebellum was removed, cut in sagittal sections and analyzed for Fos-IR to infer activation. Our results showed that the cerebellum responded with more Fos-IR in the Alm and RF groups as compared to Control. More copulatory sessions resulted in more odor-induced Fos-IR, especially in the RF group. Accordingly, we discuss possible mechanisms on how the cerebellum mediates processing of both unconditioned and conditioned odors, and how sexual experience accelerates such process.

Basolateral Amygdala Neurons Maintain Aversive Emotional Salience.

BLA neurons serve a well-accepted role in fear conditioning and fear extinction. However, the specific learning processes related to their activity at different times during learning remain poorly understood. We addressed this using behavioral tasks isolating distinct aspects of fear learning in male rats. We show that brief optogenetic inhibition of BLA neurons around moments of aversive reinforcement or nonreinforcement causes reductions in the salience of conditioned stimuli, rendering these stimuli less able to be learned about and less able to control fear or safety behaviors. This salience reduction was stimulus-specific, long-lasting, and specific to learning about, or responding to, the same aversive outcome, precisely the goals of therapeutic interventions in human anxiety disorders. Our findings identify a core learning process disrupted by brief BLA optogenetic inhibition. They show that a primary function of the unconditioned stimulus-evoked activity of BLA neurons is to maintain the salience of conditioned stimuli that precede it. This maintenance of salience is a necessary precursor for these stimuli to gain and maintain control over fear and safety behavior.SIGNIFICANCE STATEMENT The amygdala is essential for learning to fear and learning to reduce fear. However, the specific roles served by activity of different amygdala neurons at different times during learning is poorly understood. We used behavioral tasks isolating distinct aspects of learning in rats to show that brief optogenetic inhibition of BLA neurons around moments of reinforcement or nonreinforcement disrupts maintenance of conditioned stimulus salience. This causes a stimulus-specific and long-lasting deficit in the ability of the conditioned stimulus to be learned about or control fear responses. These consequences are the precisely goals of therapeutic interventions in human anxiety disorders. Our findings identify a core learning process disrupted by brief BLA optogenetic inhibition.

Mediated configural learning in rats.

Three experiments investigated mediated configural learning in male rats. In Experiment 1, after exposure to audio-visual compounds AX and BY, rats received trials where X was paired with shock, and Y was not. The idea that conditioning with X enables the evoked configural representation of AX to be linked to shock received support from the facts that while AX provoked more fear than BX, there was no difference between BY and AY. Similarly, Experiment 2 showed that after exposure to AX and BY, separate pairings of X and Y with shock resulted in more fear to AX and BY than AY and BX. In Experiment 3, rats in group consistent received separate exposures to A and X in Context C, and B and Y in D, while those in group inconsistent received A and X (and B and Y) in both C and D. After rats had received shocks in both C and D, rats in group consistent showed more fear to AX and BY than to BX and AY, but this was not the case in group inconsistent. These results indicate that configural representations, formed either by presenting auditory and visual stimuli as parts of a compound or in a shared context, are subject to a process of mediated learning.

Morphine Withdrawal Reveals Sex Differences in Contextual Responses During Cued Fear Conditioning and Extinction

Sex difference has been show in drug abuse and addiction. Previously we had found that withdrawal from chronic morphine produced a deficit in cued fear extinction learning in male rats but not in females. Thus, as result, we wanted aimed to elucidate if fear response (freezing) to the conditioning context was also different by sexsex differences were also evident for contextual fear responses. Rats were exposed to chronic morphine injections and somatic signs of spontaneous withdrawal that were assessed. at 14 and 84 hours after the last injection. Behavioral experiment Cued fear conditioning started 84 hours after the last morphine injection and consisted of three phases: conditioning, extinction and the test. Contextual fear was asses measured by analyzing a 1-min pre-tone period before the tone cue. Morphine treated males and ovariectomized females showed a tendency for increased freezing immediately upon exposure to the chamber on extinction but cycling females did not freeze significantly to the context independent of the treatment. This could suggest that in males and ovariectomized females, withdrawal alters fear circuits expression independent of the withdrawal context, but when ovarian hormones are present, fear responses might depend on re-exposure to the withdrawal context.

Anabolic–androgenic steroids impair set-shifting and reversal learning in male rats

Anabolic–androgenic steroid (AAS) abuse is prevalent not only among elite athletes, but is increasingly common in high school and collegiate sports. AAS are implicated in maladaptive behaviors such as increased aggression and risk taking, which may result from impaired cognition. Because they affect dopamine function in prefrontal cortical (PFC)-striatal circuitry, AAS may disrupt PFC-dependent processes such as behavioral flexibility. This was the focus of the present study. Adolescent male Long-Evans rats were treated chronically with high-dose testosterone (7.5mg/kg in water with 13% cyclodextrin) or vehicle sc, and tested for set-shifting and reversal-learning. For set-shifting, rats were trained on a visual cue task (VCT), then were shifted to a direction cue task (DCT), or vice-versa. For reversal learning, rats were first trained on VCT and were then required to press the opposite lever. 2-cue set-shifting introduced a novel paradigm in which rats shifted from a 1-Light Visual Task (1LVT) to a tone cue task (TCT). Testosterone-treated rats were significantly impaired on the set-shift from DCT to VCT compared to vehicle-treated controls (trials to criterion: vehicle 240.9±29.9, testosterone 388.3±59.3, p<0.05). However, on the set-shift from VCT to DCT, testosterone did not affect performance. During reversal-learning, testosterone significantly increased trials to criterion (vehicle: 495.9±91.8 trials, testosterone: 793.7±96.7 trials, p<0.05). In 2-cue set-shifting, testosterone diminished performance and the difference showed borderline significance (vehicle: 443.2±84.4 trials, testosterone: 800.4±178.2 trials, p=0.09). Our results show that testosterone impairs behavioral flexibility and have implications for understanding cognitive and behavioral changes in human AAS users.

Different expression of membrane-bound and cytosolic hippocampal steroid receptor complexes during spatial training in young male rats

Brain steroid receptors are involved in mediating stress responses and cognitive processes throughfast non-genomic signaling of membrane-bound receptors or through the slower genomic actions of cytosolic receptors. Although the contribution of these different pathways in the formation and maintenance of memories has been widely discussed, little is known about the regulation of membrane versus cytosolic receptors during a learning task. Besides the relatively well studied corticosterone-binding glucocorticoid (GR) and mineralocorticoid (MR) receptors, sex steroid hormone receptors, such as the androgen and estrogen (ERα and ERβ) receptors, have also been shown to be involved in the regulation of stress and cognition. Moreover, the latter receptors are known to be functional in both sexes. Therefore, we studied the expression of hippocampal receptors in both cellular fractions during spatial learning in male rats. Membrane and cytosolic GR were shown to be downregulated after memory acquisition and unaffected after consolidation, whereas membrane MR was upregulated after both learning phases and unaffected in the cytosol. Cytosolic ERα was downregulated after both phases and unaffected in the membrane. The remaining receptors were not regulated. The data suggest a specific role of MR and ERα during training as fast and slow mediators, respectively.

Hyperprolactinemia impairs object recognition without altering spatial learning in male rats

Prolactin (PRL) exerts protective effects on the hippocampus against chronic stress exposure, or kainic acid insults. Further, PRL null mice were recently shown to exhibit learning and memory deficits. These findings suggest the hippocampus as a PRL target. To test this hypothesis, we analyzed the hippocampal formation function in dependence of serum PRL concentrations. Male Sprague-Dawley rats were either transplanted with 2 pituitary homografts (HPRL) or had a sham operation (SHAM). Other groups were given vehicle (VEH) or daily injections of bromocriptine (BRC, 4mg/kg) to reduce PRL levels. The animals were sequentially subjected to the Morris water maze (MWM), the object recognition test and the elevated plus maze. PRL concentrations were measured with ELISAs. Learning curves from the MWM showed a progressive reduction in distance over time but no significant differences were found between SHAM and HPRL, or between BRC and VEH groups. Also, memory retrieval was not affected in the probe trial between each pair of groups. However, in the object recognition test the HPRL group failed to discriminate between novel and familiar objects, and the discrimination index was significantly reduced from that of the VEH group. BRC rats exhibited a reduced exploration of both objects compared to VEH, but had a discrimination index similar to VEH. No significant differences were observed in the EPM. In conclusion, high PRL levels impair object recognition but do not alter spatial learning. These results show for the first time that PRL impairs object recognition, and thus modulates non-spatial cognitive tasks.

Effects of acute restraint stress on set-shifting and reversal learning in male rats

Exposure to acute stress alters cognition; however, few studies have examined the effects of acute stress on executive functions such as behavioral flexibility. The goal of the present experiments was to determine the effects of acute periods of stress on two distinct forms of behavioral flexibility: set-shifting and reversal learning. Male Sprague-Dawley rats were trained and tested in an operant-chamber-based task. Some of the rats were exposed to acute restraint stress (30 min) immediately before either the set-shifting test day or the reversal learning test day. Acute stress had no effect on set-shifting, but it significantly facilitated reversal learning, as assessed by both trials to criterion and total errors. In a second experiment, the roles of glucocorticoid (GR) and mineralocorticoid receptors (MR) in the acute-stress-induced facilitation of reversal learning were examined. Systemic administration of the GR-selective antagonist RU38486 (10 mg/kg) or the MR-selective antagonist spironolactone (50 mg/kg) 30 min prior to acute stress failed to block the facilitation on reversal learning. The present results demonstrate a dissociable effect of acute stress on set-shifting and reversal learning and suggest that the facilitation of reversal learning by acute stress may be mediated by factors other than corticosterone.