Retention Session Research Articles

A Gateway between Recent and Remote Memory

A Gateway between Recent and Remote Memory

Major depression and treatment response in adolescents with ADHD and substance use disorder

Background Major depressive disorder (MDD) frequently co-occurs in adolescents with substance use disorders (SUDs) and attention deficit hyperactivity disorder (ADHD), but the impact of MDD on substance treatment and ADHD outcomes and implications for clinical practice are unclear. Methods Adolescents ( n = 303; ages 13–18) meeting DSM-IV criteria for ADHD and SUD were randomized to osmotic release methylphenidate (OROS-MPH) or placebo and 16 weeks of cognitive behavioral therapy (CBT). Adolescents with ( n = 38) and without ( n = 265) MDD were compared on baseline demographic and clinical characteristics as well as non-nicotine substance use and ADHD treatment outcomes. Results Adolescents with MDD reported more non-nicotine substance use days at baseline and continued using more throughout treatment compared to those without MDD ( p < 0.0001 based on timeline followback; p < 0.001 based on urine drug screens). There was no difference between adolescents with and without MDD in retention or CBT sessions attended. ADHD symptom severity (based on DSM-IV ADHD rating scale) followed a slightly different course of improvement although with no difference between groups in baseline or 16-week symptom severity or 16-week symptom reduction. There was no difference in days of substance use or ADHD symptom outcomes over time in adolescents with MDD or those without MDD treated with OROS-MPH or placebo. Depressed adolescents were more often female, older, and not court ordered. Conclusions These preliminary findings suggest that compared to non-depressed adolescents with ADHD and SUD, those with co-occurring MDD have more severe substance use at baseline and throughout treatment. Such youth may require interventions targeting depression.

Butyrylcholinesterase inhibitors ameliorate cognitive dysfunction induced by amyloid-β peptide in mice

The cholinesterase inhibitor, rivastigmine, ameliorates cognitive dysfunction and is approved for the treatment of Alzheimer's disease (AD). Rivastigmine is a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE); however, the impact of BuChE inhibition on cognitive dysfunction remains to be determined. We compared the effects of a selective BuChE inhibitor, N1-phenethyl-norcymserine (PEC), rivastigmine and donepezil (an AChE-selective inhibitor) on cognitive dysfunction induced by amyloid-β peptide (Aβ 1–40) in mice. Five-week-old imprinting control region (ICR) mice were injected intracerebroventricularly ( i.c.v.) with either Aβ 1–40 or the control peptide Aβ 40–1 on Day 0, and their recognition memory was analyzed by a novel object recognition test. Treatment with donepezil (1.0 mg/kg), rivastigmine (0.03, 0.1, 0.3 mg/kg) or PEC (1.0, 3.0 mg/kg) 20 min prior to, or immediately after the acquisition session (Day 4) ameliorated the Aβ 1–40 induced memory impairment, indicating a beneficial effect on memory acquisition and consolidation. In contrast, none of the investigated drugs proved effective when administrated before the retention session (Day 5). Repeated daily administration of donepezil, rivastigmine or PEC, on Days 0–3 inclusively, ameliorated the cognitive dysfunction in Aβ 1–40 challenged mice. Consistent with the reversal of memory impairments, donepezil, rivastigmine or PEC treatment significantly reduced Aβ 1–40 induced tyrosine nitration of hippocampal proteins, a marker of oxidative damage. These results indicate that BuChE inhibition, as well as AChE inhibition, is a viable therapeutic strategy for cognitive dysfunction in AD.

Training program for fundamental surgical skill in robotic laparoscopic surgery

Although the use of robotic laparoscopic surgery has increased in popularity, training protocols for gaining proficiency in robotic surgical skills are not well established. The purpose of this study was to examine a fundamental training program that provides an effective approach to evaluate and improve robotic surgical skills performance using the da Vinci(™) Surgical System. Fifteen medical students without any robotic surgical experience were recruited. Participants went through a 4-day training program for developing fundamental robotic surgical skills and received a retention test 1 day after the completion of training. Data analysis included time to task completion, average speed, total distance traveled and movement curvature of the instrument tips, and muscle activities of the participants' forearms. Surgical performance was graded by the modified Objective Structured Assessment of Technical Skills for robotic laparoscopic surgery. Finally, participants evaluated their own performance after each session through questionnaires. Significant training effects were shown for the time to task completion (p < 0.001), average speed (p < 0.01), and movement curvature (p < 0.05) for the test conditions. Significant learning effects were also found for EMG activation (p < 0.05). Participants reported more mastery, familiarity, and self-confidence and less difficulty in performing fundamental tasks with the surgical robot in both post-testing and retention sessions. Our 4-day training program comprising of a series of training tasks from fundamental to surgical skill levels was effective in improving surgical skills. Further studies are required to verify these findings with a longer period of retention.

Latent Inhibition-Related Dopaminergic Responses in the Nucleus Accumbens are Disrupted Following Neonatal Transient Inactivation of the Ventral Subiculum

Schizophrenia would result from a defective connectivity between several integrative regions as a consequence of neurodevelopmental failure. Various anomalies reminiscent of early brain development disturbances have been observed in patients' left ventral subiculum of the hippocampus (SUB). Numerous data support the hypothesis of a functional dopaminergic dysregulation in schizophrenia. The common target structure for the action of antipsychotics appears to be a subregion of the ventral striatum, the dorsomedial shell part of the nucleus accumbens. Latent inhibition, a cognitive marker of interest for schizophrenia, has been found to be disrupted in acute patients. The present study set out to investigate the consequences of a neonatal functional inactivation of the left SUB by tetrodotoxin (TTX) in 8-day-old rats for the latent inhibition-related dopaminergic responses, as monitored by in vivo voltammetry in freely moving adult animals (11 weeks) in the left core and dorsomedial shell parts of the nucleus accumbens in an olfactory aversion procedure. Results obtained during the retention session of a three-stage latent inhibition protocol showed that the postnatal unilateral functional blockade of the SUB was followed in pre-exposed TTX-conditioned adult rats by a disruption of the behavioral expression of latent inhibition and induced a total and a partial reversal of the latent inhibition-related dopaminergic responses in the dorsomedial shell and core parts of the nucleus accumbens, respectively. The present data suggest that neonatal inactivation of the SUB has more marked consequences for the dopaminergic responses recorded in the dorsomedial shell part, than in the core part of the nucleus accumbens. These findings may provide new insight into the pathophysiology of schizophrenia.

Effects of muscarinic receptor antagonism in the basolateral amygdala on two-way active avoidance

The aim of the present study was to investigate whether the blockade of muscarinic receptors (mRs) in the basolateral amygdala (BLA), which receives important cholinergic inputs related to avoidance learning, affects the consolidation of two-way active avoidance (TWAA). In Experiment 1, adult male Wistar rats were bilaterally infused with scopolamine (SCOP, 20 μg/site) or PBS (VEH) in the BLA immediately after a single 30-trial acquisition session. Twenty-four hours later, avoidance retention was tested in an identical session. Results indicated that scopolamine in the BLA did not affect TWAA performance measured by the number of avoidance responses. Experiment 2 was conducted to test whether such a negative outcome might be due to the occurrence of overtraining during acquisition, which may indeed have a protective effect against scopolamine-induced memory deficits. In this experiment, rats were infused with scopolamine in the BLA immediately after a brief 10-trial acquisition session and tested 24 h later in a 30-trial retention session. The SCOP group showed significantly more avoidances and inter-trial crossings in the retention session than the VEH rats. Together, these results reveal that mRs blockade in the BLA does not disrupt TWAA consolidation and may even enhance avoidance performance when infused after a low number of acquisition trials. Performance factors, such as locomotor activity in the shuttle-box, may account, at least in part, for the facilitative effects of muscarinic antagonism in the BLA.

The Effect of Concurrent Bandwidth Feedback on Learning the Lane-Keeping Task in a Driving Simulator

The aim of this study was to investigate whether concurrent bandwidth feedback improves learning of the lane-keeping task in a driving simulator. Previous research suggests that bandwidth feedback improves learning and that off-target feedback is superior to on-target feedback. This study aimed to extend these findings for the lane-keeping task. Participants without a driver's license drove five 8-min lane-keeping sessions in a driver training simulator: three practice sessions, an immediate retention session, and a delayed retention session I day later. There were four experimental groups (n=15 per group): (a) on-target, receiving seat vibrations when the center of the car was within 0.5 m of the lane center; (b) off-target, receiving seat vibrations when the center of the car was more than 0.5 m away from the lane center; (c) control, receiving no vibrations; and (d) realistic, receiving seat vibrations depending on engine speed. During retention, all groups were provided with the realistic vibrations. During practice, on-target and off-target groups had better lane-keeping performance than the nonaugmented groups, but this difference diminished in the retention phase. Furthermore, during late practice and retention, the off-target group outperformed the on-target group.The off-target group had a higher rate of steering reversal and higher steering entropy than the nonaugmented groups, whereas no clear group differences were found regarding mean speed, mental workload, or self-reported measures. Off-target feedback is superior to on-target feedback for learning the lane-keeping task. This research provides knowledge to researchers and designers of training systems about the value of feedback in simulator-based training of vehicular control.

Augmented Kinematic Feedback from Haptic Virtual Reality for Dental Skill Acquisition

We have developed a haptic virtual reality system for dental skill training. In this study we examined several kinds of kinematic information about the movement provided by the system supplement knowledge of results (KR) in dental skill acquisition. The kinematic variables examined involved force utilization (F) and mirror view (M). This created three experimental conditions that received augmented kinematic feedback (F, M, FM) and one control condition that did not (KR-only). Thirty-two dental students were randomly assigned to four groups. Their task was to perform access opening on the upper first molar with the haptic virtual reality system. An acquisition session consisted of two days of ten trials of practice in which augmented kinematic feedback was provided for the appropriate experimental conditions after each trial. One week after, a retention test consisting of two trials without augmented feedback was completed. The results showed that the augmented kinematic feedback groups had larger mean performance scores than the KR-only group in Day 1 of the acquisition and retention sessions (ANOVA, p<0.05). The apparent differences among feedback groups were not significant in Day 2 of the acquisition session (ANOVA, p>0.05). The trends in acquisition and retention sessions suggest that the augmented kinematic feedback can enhance the performance earlier in the skill acquisition and retention sessions.

Perceptual learning immediately yields new stable motor coordination.

Coordinated rhythmic movement is specifically structured in humans. Movement at 0° mean relative phase is maximally stable, 180° is less stable, and other coordinations can, but must, be learned. Variations in perceptual ability play a key role in determining the observed stabilities so we investigated whether stable movements can be acquired by improving perceptual ability. We assessed movement stability in Baseline, Post Training, and Retention sessions by having participants use a joystick to coordinate the movement of two dots on a screen at three relative phases. Perceptual ability was also assessed using a two-alternative forced choice task in which participants identified a target phase of 90° in a pair of displays. Participants then trained with progressively harder perceptual discriminations around 90° with feedback. Improved perceptual discrimination of 90° led to improved performance in the movement task at 90° with no training in the movement task. The improvement persisted until Retention without further exposure to either task. A control group's movement stability did not improve. Movement stability is a function of perceptual ability, and information is an integral part of the organization of this dynamical system.

Microglia Activated with the Toll-Like Receptor 9 Ligand CpG Attenuate Oligomeric Amyloid β Neurotoxicity in in Vitro and in Vivo Models of Alzheimer’s Disease

Soluble oligomeric amyloid beta (oAbeta) 1-42 causes synaptic dysfunction and neuronal injury in Alzheimer's disease (AD). Although accumulation of microglia around senile plaques is a hallmark of AD pathology, the role of microglia in oAbeta1-42 neurotoxicity is not fully understood. Here, we showed that oAbeta but not fibrillar Abeta was neurotoxic, and microglia activated with unmethylated DNA CpG motif (CpG), a ligand for Toll-like receptor 9, attenuated oAbeta1-42 neurotoxicity in primary neuron-microglia co-cultures. CpG enhanced microglial clearance of oAbeta1-42 and induced higher levels of the antioxidant enzyme heme oxygenase-1 in microglia without producing neurotoxic molecules such as nitric oxide and glutamate. Among subclasses of CpGs, class B and class C activated microglia to promote neuroprotection. Moreover, intracerebroventricular administration of CpG ameliorated both the cognitive impairments induced by oAbeta1-42 and the impairment of associative learning in Tg2576 mouse model of AD. We propose that CpG may be an effective therapeutic strategy for limiting oAbeta1-42 neurotoxicity in AD.

Postnatal functional inactivation of the entorhinal cortex or ventral subiculum has different consequences for latent inhibition‐related striatal dopaminergic responses in adult rats

Latent inhibition has been found to be disrupted in patients with acute schizophrenia. Striatal dopaminergic dysregulation is commonly acknowledged in schizophrenia. This disease may be consecutive to a functional disconnection between integrative regions, stemming from neurodevelopmental failures. Various anomalies suggesting early abnormal brain development have been described in the entorhinal cortex (ENT) and ventral subiculum (SUB) of patients. This study examines the consequences of a neonatal transitory blockade of the left ENT or left SUB for latent inhibition-related dopamine responses in the anterior part of the dorsal striatum using in-vivo voltammetry in freely moving adult rats. Reversible inactivation of both structures in different animals was achieved by local microinjection of tetrodotoxin (TTX) at postnatal day 8. Results obtained during the retention session of a three-stage latent inhibition protocol showed that the functional neonatal disconnection of the ENT or SUB caused the behavioural latent inhibition expression in pre-exposed (PE)-TTX-conditioned adult rats to disappear. After postnatal inactivation of the SUB, PE-TTX-conditioned rats displayed a reversal of the latent inhibition-related striatal dopamine responses, whereas after neonatal blockade of the ENT, dopamine changes in PE-TTX-conditioned rats monitored in the anterior striatum were between those observed in PE-phosphate-buffered-saline-conditioned and non-PE-TTX-conditioned animals. These data suggest that neonatal functional inactivation of the SUB disrupts latent inhibition-related striatal dopamine responses in adult animals more than that of the ENT. They may help improve understanding of the pathophysiology of schizophrenia.

Effects of long-term voluntary exercise on learning and memory processes: dependency of the task and level of exercise

The effect of long-term voluntary exercise (running wheel) on anxiety-like behaviour (plus maze and open field) and learning and memory processes (object recognition and two-way active avoidance) was examined on Wistar rats. Because major individual differences in running wheel behaviour were observed, the data were analysed considering the exercising animals both as a whole and grouped according to the time spent in the running wheel (low, high, and very-high running). Although some variables related to anxiety-like behaviour seem to reflect an anxiogenic compatible effect, the view of the complete set of variables could be interpreted as an enhancement of defensive and risk assessment behaviours in exercised animals, without major differences depending on the exercise level. Effects on learning and memory processes were dependent on task and level of exercise. Two-way avoidance was not affected either in the acquisition or in the retention session, while the retention of object recognition task was affected. In this latter task, an enhancement in low running subjects and impairment in high and very-high running animals were observed.

Frequency, efficiency and flexibility of indirect addition in two learning environments

This study examined the development of indirect addition as an alternative for solving multidigit subtractions, by means of two learning environments in traditionally schooled third-graders in Flanders (Belgium). Thirty-five third-graders, who did not demonstrate mastery of indirect addition, participated in an Explicit ( n = 20) or Implicit ( n = 15) learning environment that aimed to encourage the development of indirect addition. Over a period of six weeks, children participated in nine individual sessions: four practice sessions, three test sessions, one transfer session, and one retention session. The results revealed that throughout the study indirect addition was rarely used, even by the children in the explicit learning environment. However, when indirect addition was used, it was executed very efficiently.

Effects of voluntary physical exercise on learning and memory: an U-inverted relationship?

Event Abstract Back to Event Effects of voluntary physical exercise on learning and memory: an U-inverted relationship? Sílvia Garcia-Capdevila1, Isabel Portell-Cortes1, Margalida Coll-Andreu1, Meritxell Torras-Garcia1 and David Costa-Miserachs1* 1 Universitat Autònoma de Barcelona, Department of Psicobiologia i Metodologia , Spain Previous work from our laboratory suggested that voluntary exercise affected memory for a recognition object task in a U-inverted manner. To further explore this possibility rats were maintained in an standard home cage (SED) or in a home cage with an attached running wheel for 40 days. From day 1 to 11 running wheel was permanently unblocked, but from day 12 to 40, exercised animals had either the wheel unblocked only during the first 6 nightly hours (6hr) or for 18 hours (18hr) (12 nightly hours plus six daily hours). After these 40 days, a subset of animals were tested in an object recognition task with a 24 hours (RT1) and a 72 hours (RT2) retention sessions, and a different subset were sacrificed to analyse BDNF in hippocampus and perirhinal cortex. Within each condition of restricted running behaviour, we divided the animals into low- and high-runners according to the median of daily running from day 18 to 40. The final groups were 6hr-low (214 m/day), 18hr-low (472 m/day), 6hr-high (546 m/day), 18hr-high (945 m/day) and an additional group 6hr-out (4794 m/day) that includes 7 animals of the 6-hr conditions that showed a very high (outliers) running behaviour during the restriction period. 18hr-high (p=0.015) and 6hr-out (p=0.008) showed less exploration than SED in the neophobia test previous to the recognition object task. There were no differences between groups in exploration time during sample session. On RT1 none of the groups showed significant recall. On RT2 only 18hr-high group showed significant recall of the sample (p=0.009). Moreover, when considering only non-outlier subjects there was a linear relationship (p=0.039) between the amount of exercise and the object recognition memory on RT2, but when including the outlier subjects the relationship was U-inverted (p=0.038). Regarding BDNF, levels of the protein were nearly undetectable in the perirhinal cortex of most of the animals. BDNF levels in the hippocampus showed no differences between groups. Conference: 41st European Brain and Behaviour Society Meeting, Rhodes Island, Greece, 13 Sep - 18 Sep, 2009. Presentation Type: Poster Presentation Topic: Poster presentations Citation: Garcia-Capdevila S, Portell-Cortes I, Coll-Andreu M, Torras-Garcia M and Costa-Miserachs D (2009). Effects of voluntary physical exercise on learning and memory: an U-inverted relationship?. Conference Abstract: 41st European Brain and Behaviour Society Meeting. doi: 10.3389/conf.neuro.08.2009.09.154 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 09 Jun 2009; Published Online: 09 Jun 2009. * Correspondence: David Costa-Miserachs, Universitat Autònoma de Barcelona, Department of Psicobiologia i Metodologia, Barcelona, Spain, david.costa@uab.cat Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Sílvia Garcia-Capdevila Isabel Portell-Cortes Margalida Coll-Andreu Meritxell Torras-Garcia David Costa-Miserachs Google Sílvia Garcia-Capdevila Isabel Portell-Cortes Margalida Coll-Andreu Meritxell Torras-Garcia David Costa-Miserachs Google Scholar Sílvia Garcia-Capdevila Isabel Portell-Cortes Margalida Coll-Andreu Meritxell Torras-Garcia David Costa-Miserachs PubMed Sílvia Garcia-Capdevila Isabel Portell-Cortes Margalida Coll-Andreu Meritxell Torras-Garcia David Costa-Miserachs Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Effect of reversible inactivation of locus ceruleus on spatial reference and working memory

The locus coeruleus (LC) is the largest source of norepinephrine (NE) in the prefrontal cortex and the hippocampus, influencing the cognitive functions of these areas. All previous studies have studied the role of the LC–NE system on learning and memory using the irreversible lesion technique, employing either electrocoagulation or excitotoxins. However, the reversible functional inactivation of LC by means of stereotaxic local microinjection of lidocaine could measure the phases of memory processing (acquisition, consolidation and retention) without any interference with the other cognitive functions of the same structure either during earlier or later phases of the same process. The aim of this study is to investigate LC involvement in spatial reference and working memory by inducing bilateral pre-training, post-training and pre-retrieval lidocaine functional inactivation using the Morris water maze task. The reversible inactivation of LC was applied at different stages of spatial memory formation: (1) immediately before the training sessions to determine the effects on acquisition of the both reference and working memory; (2) immediately after the training session to evaluate effects on both spatial memory consolidation and retention of working memory; and (3) immediately before the 24 h retention session to analyze the effects on the retrieval process of reference memory. Our results indicate that the bilateral reversible inactivation of LC significantly impaired the acquisition of reference and working memory, while it had no effect on consolidation and/or retention of such memories in the Morris water maze (MWM) task. Therefore, the noradrenergic system of the LC may play a more important role in acquisition than in consolidation and retrieval of spatial memory in wistar rats.

Differential influence of the ventral subiculum on dopaminergic responses observed in core and dorsomedial shell subregions of the nucleus accumbens in latent inhibition

It has previously been reported that dopamine (DA) responses observed in the core and dorsomedial shell parts of the nucleus accumbens (Nacc) in latent inhibition (LI) are dependent on the left entorhinal cortex (ENT). The present study was designed to investigate the influence of the left ventral subiculum (SUB) closely linked to the ENT on the DA responses obtained in the Nacc during LI, using an aversive conditioned olfactory paradigm and in vivo voltammetry in freely moving rats. In the first (pre-exposure) session, functional blockade of the left SUB was achieved by local microinjection of tetrodotoxin (TTX). In the second session, rats were aversively conditioned to banana odor, the conditional stimulus (CS). In the retention (test) session the results were as follows: (1) pre-exposed (PE) conditioned animals microinjected with TTX, displayed aversion toward the CS; (2) in the core part of the Nacc, for PE-TTX-conditioned rats as for non-pre-exposed (NPE) conditioned animals, DA levels remained close to the baseline whereas DA variations in both groups were significantly different from the DA increases observed in PE-conditioned rats microinjected with the solvent (phosphate-buffered saline (PBS)); (3) in the shell part of the Nacc, for PE-TTX-conditioned rats, DA variations were close to or above the baseline. They were situated between the rapid DA increases observed in NPE-conditioned animals and the transient DA decreases obtained in PE-PBS-conditioned animals. These findings suggest that, in parallel to the left ENT, the left SUB controls DA LI-related responses in the Nacc. The present data may also offer new insight into the pathophysiology of schizophrenia.

Effects of cholinesterase inhibitor metrifonate on naive rats and rats with a model of hypoxia-induced impaired memory

Abstract Cholinesterase inhibitors are currently used in the therapy of different kind of dementia to improve brain memory functions. The acetylcholinesterase inhibitor metrifonate was studied in naive rats and in rats with a model of sodium nitrite-induced hypoxia. One active avoidance test and in two passive avoidance tests were used. In the active avoidance test metrifonate increased the number of avoidances during the learning session only. In both passive avoidance tests, metrifonate prolonged latency differently during the learning session and in short-term or in long-term memory retention. Hypoxic rats showed lower numbers of avoidances in learning and memory retention sessions. Metrifonate increased the number of avoidances during the learning session for hypoxic rats. In the step-through passive avoidance test, metrifonate increased the latency of reactions in the learning session and in long-term memory retention tests. In the step-down passive avoidance test, the groups with hypoxia and metrifonate did not change the latency of reaction in the learning and long-term memory retention sessions, but increased the latency of reactions in the short-term memory retention test. Morphological data showed a significant impaired neuronal structure in a CA1 zone of the hippocampus in hypoxic rats and a tendency to preserving in rats treated with metrifonate. Our results suggest that metrifonate improves cognitive functions in naive and in hypoxic rats.

7-Nitroindazole, a neuronal nitric oxide synthase inhibitor, impairs passive-avoidance and elevated plus-maze memory performance in rats

The role of nitric oxide (NO) on cognitive performance in a modified elevated plus-maze (mEPM) and passive-avoidance (PA) task was investigated by using the NO synthase (NOS) inhibitor 7-nitroindazole (7-NI) and an NO precursor l-arginine. The interaction between the activation of N-methyl- d-aspartate (NMDA) receptors and NO synthesis on memory retention was also studied. 7-NI, l-arginine or MK-801, a non-competitive NMDA receptor antagonist were injected intraperitoneally (i.p) to male Wistar rats 30 min before the first training session of the PA test or 30 min before on the first day testing (acquisition session) of mEPM task. Transfer latency, the time rat took to move from the open arm to the enclosed arm, was used as an index of learning and memory in a mEPM test. The retention session was performed 24 h after the acquisition one. In the PA task, the retention test was carried out 24 h after training and reduction of retention latency was used to evaluate the acquisition of learning and memory. Blood glucose level and locomotor activity of the rats was also evaluated. 7-NI (10, 20, 25, 50 mg/kg) and MK-801 (0.15 mg/kg) significantly prolonged the transfer latency on retention session in a mEPM test and shortened step-through latency in PA test. 7-NI-induced impairment in memory and learning was partly reversed by l-arginine (200 mg/kg), a competitive substrate for NOS. However subeffective doses of 7-NI (5 mg/kg) and MK-801 (0.075 mg/kg) given in combination significantly impaired plus-maze and PA performances in rats. Thus NMDA receptor mediated NO pathways may be implicated in the PA and mEPM behaviours in rats. Since 7-NI does not affect blood pressure and did not alter blood glucose level and locomotor activity in conscious rats, 7-NI-induced impairment of memory is not due to either hypertension, changes in blood glucose level or effects on locomotor activity.

Dopamine D2/D3 Receptors Play a Specific Role in the Reversal of a Learned Visual Discrimination in Monkeys

Converging evidence supports a role for mesocorticolimbic dopaminergic systems in a subject's ability to shift behavior in response to changing stimulus-reward contingencies. To characterize the dopaminergic mechanisms involved in this function, we quantified the effects of subtype-specific dopamine (DA) receptor antagonists on acquisition, retention, and reversal of a visual discrimination task in non-human primates (Chlorocebus aethiops sabaeus). We used a modified Wisconsin General Test Apparatus that was equipped with three food boxes, each fitted with a lid bearing a unique visual cue; one of the cues concealed a food reward, whereas the other two concealed an empty box. The monkeys were trained first to acquire a novel discrimination (eg A(+), B(-), C(-)) in a single session, before experiencing either a reversal of the discrimination (eg A(-), B(+), C(-)) or the acquisition of a completely new discrimination (eg D(+), E(-), F(-)), on the following day. Systemic administration of the D(2)/D(3) receptor antagonist raclopride (0.001-0.03 mg/kg) failed to significantly affect the performance of reversal learning when reversal sessions were run without a retention session. But, raclopride (0.03 mg/kg) significantly impaired performance under the reversal condition when reversal sessions were run right after a retention session; however, it did not affect acquisition of a novel visual discrimination. Specifically, raclopride significantly increased the number of reversal errors made before reaching the performance criterion in the reversal, but not in new learning sessions. In contrast, the D(1)/D(5) receptor antagonist SCH 23390 did not significantly modulate acquisition of a novel discrimination or reversal learning at doses (0.001-0.03 mg/kg, i.m.) that did not suppress behavior generally. In addition, none of the drug treatments affected retention of a previously learned discrimination. The results strongly suggest that D(2)/D(3) receptors, but not D(1)/D(5) receptors, selectively mediate reversal learning, without affecting the capacity to learn a new stimulus-reward association. These data support the hypothesis that phasic DA release, acting through D(2)-like receptors, mediates behavioral flexibility.

Muscarinic cholinergic receptor blockade in the rat prelimbic cortex impairs the social transmission of food preference

Previous findings demonstrate the involvement of the cholinergic NBM in the acquisition of the social transmission of food preference (STFP), a relational associative odor-guided learning task. There is also evidence that muscarinic receptors in the medial prefrontal cortex, an important NBM target area, may modulate olfactory associative memory. The present experiment determined the consequences of blocking muscarinic cholinergic receptors in a component of the medial prefrontal region (the prelimbic cortex) on the STFP task. Adult male Wistar rats were bilaterally infused with scopolamine (20 μg/site) prior to training and showed a severe impairment in the expression of the task measured in two retention sessions, both immediately and 24 h after training. Local scopolamine injections in the prelimbic cortex did not affect other behavioral measures such as olfactory perception, social interaction, motivation to eat, neophobia, or exploration. Results suggest that muscarinic transmission in the prelimbic cortex is essential for the STFP, supporting the hypothesis that ACh in a specific prefrontal area is important for this naturalistic form of olfactory relational memory. Current data are discussed in the context of disruption of learning as a result of interferences in PLC functions such as behavioral flexibility, attention, and strategic planning.