Response Learning Task Research Articles

Estradiol impairs response inhibition in young and middle-aged, but not old rats

Estrogens have been shown to have a strong influence on such cognitive domains as spatial memory, response learning, and several tasks of executive function, including both working memory and attention. However, the effects of estrogens on inhibitory control and timing behavior, both important aspects of executive function, have received relatively little attention. We examined the effects of estradiol on inhibitory control and timing behavior using a differential reinforcement of low rates of responding (DRL) task. Ovariectomized young (3 month), middle-aged (12 month), and old (18 month) Long–Evans rats were implanted with Silastic implants containing 0, 5 or 10% 17β-estradiol in cholesterol vehicle and were tested on a DRL task requiring them to wait 15 s between lever presses to receive a food reinforcer. The ratio of reinforced to non-reinforced lever presses did not differ across age in the cholesterol vehicle group. Conversely, 17β-estradiol impaired learning of the DRL task in young and middle-aged rats, but the learning of old rats was not impaired relative to vehicle controls following either 5% or 10% 17β-estradiol treatment. Overall, old rats also made fewer lever presses than both the young and middle-aged rats. These results provide new evidence that estrogens impair inhibitory control, an important aspect of self regulation, and add to existing evidence that estrogens differentially affect cognition at different ages.

Differentiation of MDMA or 5-MeO-DIPT induced cognitive deficits in rat following adolescent exposure.

The so-called club Foxy or Methoxy Foxy (5-Methoxy-N,N-di(iso)propyltryptamine hydrochloride; 5-MeO-DIPT) is a newer drug of abuse that has recently gained in popularity among recreational users as an alternative to MDMA (Ecstasy). While considerable research into the consequences of MDMA use is available, much remains unknown about the neurobiological consequences of 5-MeO-DIPT use. In the present study, beginning at 35 days of age adolescent rats were given repeated injections of 10 mg/kg of 5-MeO-DIPT, MDMA, or a corresponding volume of isotonic saline. Adult animals (135 days old) were trained and tested on a number of tasks designed to assess the impact, if any, and severity of 5-MeO-DIPT and MDMA, on a series of spatial and nonspatial memory tasks. Both the 5-MeO-DIPT- and the MDMA-treated rats were able to master the spatial navigation tests where the task included a single goal location and all groups performed comparably on these phases of training and testing. Conversely, the performance of both groups of the drug-treated rats was markedly inferior to that of the control animals on a task where the goal was moved to a new location and on a response learning task, suggesting a lack of flexibility in adapting their responses to changing task demands. In addition, in a response learning version of a learning set task, 5-MeO-DIPT rats made significantly more working memory errors than MDMA or control rats. Results are discussed in terms of observed alterations in serotonin activity in the forebrain and the consequences of compromised serotoninergic systems on cognitive processes.

Cortico-limbic–striatal contribution after response and reversal learning: A metabolic mapping study

Learning of arbitrary stimulus–response associations is an adaptive behavior essential for species survival in an ever-changing environment. Particular subdivisions of the striatum have been shown to be critical for both motor–response learning and reversal learning. However, recent evidence suggests that different cortical and subcortical brain regions may be involved in response learning, a kind of learning more complex than previously thought. In fact, many brain regions subserving response learning seem to be also related to reversal learning, traditionally ascribed to the prefrontal cortex. The present study examined the role of different subdivisions of the rat prefrontal cortex, striatum, amygdala and the ventral tegmental area on both response and reversal learning evaluated in the water T-maze. Increased neuronal metabolic activity, as measured by cytochrome oxidase (CO) histochemistry, was found in most brain regions after training rats in a response learning task as compared to yoked controls. Reversal learning was associated with a return to baseline CO activity levels except for the orbitofrontal cortex and the ventral tegmental area. Analysis of functional connectivity among brain regions showed significant correlations in CO activity between particular cortical and striatal subdivisions in the reversal learning group. These findings suggest that the interaction of specific frontal and subcortical regions is required for reversal but not for response learning. However, our findings support the involvement of a cortico-limbic–striatal circuit in both types of learning.

Peripheral anxiogenic drug injections differentially affect cognitive and habit memory: role of basolateral amygdala

Findings from single-solution plus-maze tasks that require the use of either place or response learning indicate that post-training intra-basolateral amygdala (BLA) administration of the anxiogenic α-2 adrenoreceptor antagonist RS 79948 can both enhance dorsal striatal-dependent response learning and impair hippocampus-dependent place learning. Whether post-training peripheral administration of RS 79948 can also enhance and impair response and place learning respectively, is not known. If peripheral drug administration can also produce this “dual” effect on cognitive and habit memory, it would be of interest to know whether the functional integrity of the BLA is critical. In order to examine these questions, the present experiments combined peripheral administration of RS 79948 with concurrent neural inactivation of the BLA. Adult male Long–Evans rats were trained in place or response learning tasks in a water plus-maze. On days 1–3 of training, rats received post-training peripheral injections of saline or RS 79948 (0.1 mg/kg) combined with intra-BLA injections of saline or the sodium channel blocker bupivacaine (1.0% solution, 0.5 μl). Post-training peripheral injections of RS 79948 enhanced acquisition of response learning, and impaired acquisition of place learning. Bupivacaine infusions into the BLA had no effect on acquisition of either task. However, intra-BLA infusions of bupivacaine blocked both the enhancement of response learning and the impairment of place learning produced by RS 79948. Taken together, the findings indicate that although the functional integrity of BLA is not necessary for acquisition of place and response learning, BLA activity is critical in order for peripheral injections of an anxiogenic drug to differentially modulate hippocampus-dependent and dorsal striatal-dependent memory.

Effects of morphine withdrawal on place learning and response learning in rats

Objective To investigate the effects of morphine withdrawal on place learning and response learning in rat. Methods 48 wistar rats were divided into morphine-withdrawal group,morphine-maintenance group and saline group. First,the morphine-withdrawal group and morphine-maintenance group both received morphine pretreatment (SC 5mg.kg-1.day-1) for 6 days,and the saline group received saline injection in the same time. Then all the animals were trained with the place learning task or the response learning task in water plus maze. The morphine-maintenance group received morphine daily between two trains,and the morphine-withdrawal groups and saline group received saline in the same time. Results In the place learning task ,the correction rate of the morphine-withdrawal group,morphine-maintenance group and saline group was (97.0±6.0)%,(79.9±20.1)% and (61.0±20.6)% respectively .The difference between morphine-withdrawal group and saline group was significantly ( P <0.01 ).Accordingly,the difference in training effect was significant between these two groups by repeated measure with analysis of variance ( F =31.196,P <0.01). Resemble results were found in the place reverse learning task. There was no significant difference in three groups in response learning task and response reverse learning task. Conclusion Morphine withdrawal may increase place learning,with no significant improvement in response learning. Key words: Place learning; Response learning; Morphine withdrawal; Rewarding effect

Frontal operculum temporal difference signals and social motor response learning

Substantial experimental evidence supports the theory that the dopaminergic system codes a phasic (short duration) signal predicting the delivery of primary reinforcers, such as water when thirsty, during Pavlovian learning. This signal is described by the temporal difference (TD) model. Recently, it has been suggested that the human dopaminergic system also codes more complex cognitive goal states, including those required for human social interaction. Using functional magnetic resonance imaging (fMRI) with 18 healthy subjects, we tested the hypothesis that TD signals would be present during a Pavlovian learning task, and during a social motor response learning task. Using an identical model, TD signals were present in both tasks, although in different brain regions. Specifically, signals were present in the dorsal anterior cingulate, ventral striatum, amygdala, and thalamus with Pavlovian learning, and the dorsal anterior cingulate and bilateral frontal operculum with social motor response learning. The frontal operculum is believed to be the human homologue of the monkey mirror neuron system, and there is evidence which links the region with inference about other peoples' intentions and goals. The results support the contention that the human dopaminergic system predicts both primary reinforcers, and more complex cognitive goal states, such as motor responses required for human social group interaction. Dysfunction of such a mechanism might be associated with abnormal affective responses and incorrect social predictions, as occur in psychiatric disorders.

An Examination of the Effects of 5-Methoxy-N,N-di(iso)propyltryptamine Hydrochloride (Foxy) on Cognitive Development in Rats

The hallucinogenic "designer drug" known as Foxy or Methoxy Foxy and formally know as 5-Methoxy-N,N-di(iso)propyltryptamine hydrochloride (5-MeO-DIPT) is rapidly gaining popularity among recreational users. However, little is known about the consequences of its use on neuropsychological development or behavior. During one of two adolescent periods, the rats were given repeated injections of either saline or 5 mg/kg of 5-MeO-DIPT. Once the animals reached 80 days of age, they were trained and tested on a number of tasks designed to assess the effects of 5-MeO-DIPT, if any, on memory tasks with spatial components that presumably involve declarative memory systems and on a nonspatial task that is considered sensitive to disruptions in nondeclarative memory. With one exception, both the 5-MeO-DIPT- and saline-treated rats were able to master the spatial navigation tests at comparable rates. However, the performance of the drug-treated rats was markedly inferior to that of the control animals on a response-learning task, suggesting a lack of flexibility in adapting their responses to changing task demands. This could indicate reductions in serotonin activity in the forebrain similar to the effects of studied drugs such as methylenedioxymethamphetamine (MDMA), suggesting 5-MeO-DIPT may act as a toxin compromising serotoninergic systems in the brain.

Differential effects of estrogen on hippocampal- and striatal-dependent learning

Estrogen’s role in learning and memory may be to predispose animals to use specific cognitive strategies ( Korol & Kolo, 2002). Specifically, estrogen may facilitate hippocampal-dependent learning, while at the same time attenuate striatal-dependent learning. As a stringent test of this hypothesis, place or response learning on an eight-arm radial maze was compared between ovariectomized (OVX) female Long–Evans rats and rats with chronic estrogen replacement (OVX + E; 5 mg 17-β estradiol 60-day release tablet). Reference and working memory errors were monitored separately for both place and response learning tasks. OVX + E rats learned the place task significantly faster than the response task, and faster than OVX rats. OVX rats required fewer days to reach criterion on the response task than OVX + E rats. Estrogen selectively enhanced reference memory performance, but only during place learning. The specific pattern of estrogen effects on learning suggests that future studies include verification of cognitive strategies used by animals.

Estrogen increases the sensitivity of ovariectomized rats to the disruptive effects produced by antagonism of D 2 but not D 1 dopamine receptors during performance of a response learning task

Estrogen impairs performance on some striatum-sensitive tasks of learning and memory. Evidence indicates that it may have these impairing effects by creating a bias to use hippocampally based strategies to solve tasks whether or not it is advantageous to do so. Estrogen may also exert direct effects in the striatum to affect performance on striatum-mediated procedural memory tasks. In spite of the robust effects that estrogen exerts on nigrostriatal dopaminergic neurons, the role of dopamine in the estrogen-induced effects on procedural memory tasks remains unexplored. The goal of the present study was to assess the independent and interactive effects of estrogen and dopamine antagonists on a striatum-mediated response learning task. Adult rats were ovariectomized and implanted with Silastic capsules containing 25% estradiol diluted in cholesterol or 100% cholesterol. Rats were trained to receive food rewards in an elevated plus maze by making a specified response (right or left turn). Following acquisition, dose–effect curves were determined for the D 1 dopamine receptor antagonist, SCH 23390, and the D 2 dopamine receptor antagonist, eticlopride. Estrogen did not significantly affect acquisition of the task and had no significant effect on the ability of SCH 23390 to disrupt performance on the task. However, estrogen significantly increased the sensitivity of the rats to the error-increasing effects of eticlopride. These results indicate that estrogen may differentially interact with D 1 and D 2 dopamine receptors to affect response learning. They also suggest that in addition to creating a bias to use hippocampally based strategies to solve tasks, estrogen may affect performance on procedural memory tasks through direct action on dopaminergic functioning.

Place and Response Learning of Rats in a Morris Water Maze: Differential Effects of Fimbria Fornix and Medial Prefrontal Cortex Lesions

The question examined in this study is concerned with a possible functional dissociation between the hippocampal formation and the prefrontal cortex in spatial navigation. Wistar rats with hippocampal damage (inflicted by a bilateral lesion of the fimbria fornix), rats with damage to the medial prefrontal cortex, and control-operated rats were examined for their performance in either one of two different spatial tasks in a Morris water maze, a place learning task (requiring a locale system), or a response learning task (requiring a taxon system). Performance of the classical place learning (allocentric) task was found to be impaired in rats with lesions of the fimbria fornix, but not in rats with damage of the medial prefrontal cortex, while the opposite effect was found in the response learning (egocentric) task. These findings are indicative of a double functional dissociation of these two brain regions with respect to the two different forms of spatial navigation. When the place learning task was modified by relocating the platform, the impairment in animals with fimbria fornix lesions was even more pronounced than before, while the performance of animals with medial prefrontal cortex lesions was similar to that of their controls. When the task was again modified by changing the hidden platform for a clearly visible one (visual cue task), the animals with fimbria fornix lesions had, at least initially, shorter latencies than their controls. By contrast, in the animals with medial prefrontal cortex damage this change led to a slight increase in escape latency.

Response-contingent variation in visual recall: Evidence of a dynamic memory trace.

Sixty-six subjects learned responses to four ellipses (eccentrically 0.52) which varied orthogonally in area (two large: 994 mm2; two small: 671 mm2) and orientation (two with major axis vertical, two with major axis horizontal). Correct responses were contingent on either the area or the orientation of the ellipses. After learning the correct responses, subjects recalled the ellipses by drawing them. Recall was either immediately, 1 day, or 2 weeks after learning the responses. The recall drawings were measured for area and for orientation (ratio of the length of the vertical to the horizontal axis). Differences among the recall drawings increased on the dimension (area or orientation) which was associated with correct responses during the learning task. The differences on the associated dimension were large when recall was tested immediately after the response learning task, small when recall was tested 1 day after learning, and large again when recall was tested 2 weeks after learning the responses. This experiment eliminated one potential source of uncontrolled variability in earlier results. The results are consistent with previous experiments and suggest an active two-phase memory consolidation process extended over time.