Hippocampal seizures disrupt working memory performance but not reference memory acquisition.

The effect of hippocampal seizures in rats was assessed in two spatial memory tasks: The reference memory task was a simultaneous two-choice discrimination in a T-maze. The working memory task was a delayed conditional discrimination in a radial arm maze. In each task the hippocampus of each rat was stimulated to seizure after the presentation of the information to be remembered. In the reference memory task, hippocampal seizures did not impair acquisition, whether the stimulation was given immediately after or 4 hr after the presentation of the stimuli to be remembered. In the working memory task, hippocampal seizures did impair performance in a group of the same rats. These results support the distinction between a trial-dependent working memory system that requires hippocampal function and a trial-independent memory system that does not depend on hippocampal function. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Antagonism of NMDA receptors but not AMPA/kainate receptors blocks bursting in dopaminergic neurons induced by electrical stimulation of the prefrontal cortex

Evidence suggests that the prefrontal cortex (PFC) plays an important role in the burst activity of midbrain dopaminergic (DA) neurons. In particular, electrical stimulation of the PFC elicits patterns of activity in DA neurons, closely time-locked to the stimulation, which resemble natural bursts. Given that natural bursts are produced by the activity of excitatory amino acid (EAA)-ergic afferents, if PFC-induced time-locked bursts are homologues of natural bursts, EAA antagonists should attenuate them. Hence, the NMDA (N-methyl-D-aspartate) antagonist CPP (3-((+/-)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid) and the AMPA (D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxalone propionic acid)/kainate antagonist CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) were applied by iontophoresis to DA neurons exhibiting time-locked bursts during PFC stimulation. CPP produced a significant reduction in time-locked bursting. In contrast, CNQX (at currents which antagonised AMPA responses) did not. These effects of CPP and CNQX on time-locked bursting mirror the effects previously reported for these drugs on natural bursting. Since natural bursting and bursting induced by PFC stimulation are both blocked selectively by CPP, the present results increase the degree of analogy between the two burst phenomena, thereby adding extra support to the contention that the cortex is involved in producing the natural bursting in DA neurons.     

Early acquisition, but not retention, of the classically conditioned eyeblink response is N-methyl-D-aspartate (NMDA) receptor dependent

N-methyl-D-aspartate (NMDA) antagonists impair performance in some tasks, but whether they impair learning directly or through effects on sensorimotor performance remains controversial. Rats administered a competitive NMDA antagonist, CGP-39551, 24 hr before training could not acquire a classically conditioned eyeblink response. The associative deficit remained evident during training with a high-intensity conditioned stimulus, even though sensory reactivity was unaffected. The antagonist did not alter retention and thus did not affect motor performance of the task. These results extend and confirm studies that implicate NMDA-receptor activation in the acquisition of classically conditioned associations and specifically in tasks not dependent on the hippocampus for learning itself. Moreover, they substantiate recent claims that NMDA receptor activation (and by association, long-term potentiation) may be involved in early processes of procedural memory formation.     

Scopolamine injection into the olfactory bulb impairs short-term olfactory memory in rats.

A previous experiment showed that systemic administration of the muscarinic antagonist scopolamine altered delayed matching in an olfactory task in rats. The present experiment tested whether the impairment could result from blockade of the cholinergic transmission in the first relay structure of the olfactory system, the olfactory bulb. 25 rats served as Ss. The drug was infused directly into both olfactory bulbs before test sessions. Results show that the intrabulbar infusion reproduced the effect of the systemic administration. With a 4-sec delay between target odor and choice test, performances of treated rats remained unchanged; however, with a 30-sec delay, rats performed randomly. Results from a complementary electrophysiological experiment in anesthetized rats support the idea that scopolamine injected into the olfactory bulb was unlikely to have reached more central structures. Further evidence for the involvement of pure sensory areas in short-term memory is concluded. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Adaptation of cortical but not hippocampal NMDA receptors after chronic citalopram treatment

Forty three cases of astrocytic tumors and mixed gliomas were studied with the aim of evaluating the reproducibility of the Kernohan grading system vis a vis (a) grading using computer-aided malignancy classifier TESTAST 268 and (b) grading by quantitative morphometric evaluation of the various histological parameters of TESTAST 268. These patients were then followed up for variable periods with a maximum of forty months. High inter and intra-observer variability were observed in the Kernohan grading system. TESTAST 268 was found to be simpler, rapid and more reproducible. However, one drawback observed of this system was that it did not completely eliminate inter-observer variability because there was still some subjectivity in assignment of the categorical values against the histological features. Morphometric evaluation of the semi-quantitative assignment values of the 4 histological variables in the TESTAST 268 classifier using Zeiss Morphomat-30 revealed a statistically significant difference between the clusters of the measured quantitative values. A repeat grading using TESTAST 268 and categorical assignment values of histological features derived from the absolute values obtained by morphometry resulted in complete elimination of inter-observer variability. Thus, this study highlights the importance of objectivisation using TESTAST 268 and histologic morphometry in the grading of gliomas. However, since this is a preliminary study on a small number of cases, no cut off values of these measurements have been proposed.     

Fornix transection impairs visuospatial memory acquisition more than retrieval.

It has been hypothesized that some fornical fibres may instantiate a neuromodulatory reinforcement signal supporting memory acquisition in medial temporal cortical regions. This suggests that fornix transection should impair postoperative new learning more severely than the recall of preoperatively acquired information. Here, postoperative recall of 288 concurrent visuo-spatial discrimination problems acquired preoperatively was unaffected after fornix transection in the macaque, whereas new postoperative learning of 72 problems was impaired. This and other recent evidence supports the idea that the main function of the fornix in macaque monkeys is to support new learning about spatio-temporal context. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Partial hippocampal kindling affects retention but not acquisition and place but not cue tasks on the radial arm maze

The performance of rats that were partially kindled in the hippocampus was assessed on an 8-arm radial arm maze with 4 baited arms. In rats first trained and then kindled, deficits were found on a place task in which rats reached the goal arms of the maze using salient extramaze spatial cues, but not on an intramaze cue task in which rats reached the goal arms using salient intramaze cues. Acquisition of a new place task on the maze was not different between kindled and control rats. In conclusion, partial hippocampal kindling disrupted the retention but not the acquisition of a spatial or place task; retention of a nonspatial cue task was not disrupted.     

Hippocampectomy impairs the memory of recently, but not remotely, acquired trace eyeblink conditioned responses.

New Zealand male rabbits (Oryctolagus cuniculus) were trained on a trace eyeblink conditioning paradigm using a 250-ms tone conditioned stimulus, a 100-ms airpuff unconditioned stimulus, and a 500-ms trace interval. Rabbits received bilateral hippocampal aspirations either 1 day or 1 month after learning. Controls consisted of time-matched sham-operated and neocortical aspirated rabbits. When retested on the trace paradigm, rabbits with hippocampal aspirations 1 day after learning were significantly and substantially impaired in the retention of trace conditioned responses. In contrast, rabbits that received hippocampal aspirations 1 month after training retained trace conditioned responses at a level comparable to that of the controls. Moreover, hippocampectomy had no effect on the retention of delay eyeblink conditioning. Thus, the hippocampus appears to be necessary for the retention of recently acquired, but not remotely acquired, trace conditioned responses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Loneliness impairs daytime functioning but not sleep duration.

Objective: To assess the prospective association between daily feelings of loneliness and subsequent feelings of daytime dysfunction indicative of poor sleep quality. Design: Three consecutive end-of-day diaries were completed by a population-based sample of 215 adults (mean age = 57.5 years, SD = 4.4). Diary questions probed sleep duration, daytime dysfunction (i.e., fatigue, low energy, sleepiness), loneliness, physical symptoms, and depressed affect experienced that day. Chronic health condition data and body mass index were also obtained. Autoregressive cross-lagged panel models were used to examine the magnitude of reciprocal prospective associations between loneliness and daytime dysfunction. Main Outcome Measures: Unstandardized path coefficients adjusted for race/ethnicity, sleep duration, marital status, household income, chronic health conditions, and health symptom severity. Results: Daily variations in loneliness predicted subsequent feelings of daytime dysfunction (B = 0.16, p     

Antagonism at delta opioid receptors blocks cocaine's, but not morphine's, enhancement of responding for intracranial stimulation.

Rats were fixed with a chronically indwelling bipolar electrode for direct electrical stimulation of the medial forebrain bundle as it courses through the lateral hypothalamus. In Experiment 1, the rats were trained to self-stimulate (i.e., lever press) at each of 3 intensities of intracranial stimulation (ICS) for 10 min daily. In Experiment 2, only 2 intensities were offered. After stable daily rates of responding for each intensity of ICS were established, rats received either cocaine (5 or 10 mg/kg) or morphine (4 mg/kg) daily. Both cocaine and morphine significantly increased rates of responding. Naltrindole (NTI; 10 mg/kg) reduced rats' rates of responding under cocaine to those observed under vehicle. NTI had very little impact on morphine's effects. These data support the conclusion that selective 8 opioid receptor antagonists may be useful for treating cocaine addiction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cholinergic lesion of the striatum impairs acquisition and retention of a passive avoidance response.

Significant impairments in the acquisition and retention of a step-down passive avoidance task were found in Sprague-Dawley rats with striatal lesions induced by the cholinergic neurotoxin AF64A. No significant differences between control and AF64A-injected Ss were found in sensitivity to electric shock or in various measures of spontaneous locomotor activity. Striatal choline acetyltransferase (CAT) activity was significantly decreased in AF64A-treated Ss compared to controls, whereas glutamic acid decarboxylase (GAD) activities were not. Furthermore, there were no significant differences between groups in CAT and GAD in either the cortex or the hippocampus, supporting the specificity of the lesion to the striatum. The passive avoidance deficits support a role for the striatal cholinergic system in complex behavioral processes. (14 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Involvement of mechanisms dependent on NMDA receptors, nitric oxide and protein kinase A in the hippocampus but not in the caudate nucleus in memory

The effects of the NMDA receptor antagonist AP5, the nitric oxide synthase (NO) inhibitor NO-arg or the protein kinase A (PKA) inhibitor KT5720 on memory were evaluated. Rats bilaterally implanted in the CA1 region of the dorsal hippocampus were trained and tested in a step-down inhibitory avoidance task, and rats unilaterally implanted in the left posteroventral region of the caudate nucleus were trained and tested in a cued water maze task. Previous findings from this and other laboratories had found that lesions or pharmacological treatments of these sites significantly altered memory of these two tasks. Immediately after training, animals received intrahippocampal or intracaudate 0.5 microliter microinfusions of saline, AP5, NO-arg or KT5720. All three drugs impaired retention of inhibitory avoidance, but did not affect retention of the cued water maze. The findings suggest that NMDA receptor-, NO- and PKA-mediated processes in the dorsal hippocampus, but not in the caudate nucleus, are involved in memory.     

Scopolamine impairs object exploration but not habituation in rats

Memory of a novel object was examined in saline (Sal) and scopolamine (Scopo) treated rats (1.0 mg/kg). Scopo rats showed lower overall exploration time than Sal rats, resulting mainly from shorter durations per contact. In a second exposure to the same object, after 1 min or 20 min interval, both groups displayed marked decrease of exploration indicating between-session habituation. The shorter time spent by Scopo rats on investigation of an object during a single approach might be interpreted as a deficit in maintenance of attention. Nevertheless, Scopo rats were able to acquire sufficient information for the retention during 20 min interval, as indicated by habituation, which is an elementary index of memory.     

Cholinergic blockade in the rat impairs strategy selection but not learning and retention of nonspatial visual discrimination problems in a swimming pool.

A procedure was developed to study black versus white and horizontal versus vertical pattern visual discriminations in a swimming pool. The effects of central cholinergic muscarinic receptor blockade by atropine sulfate was then evaluated. The drug treatment impaired acquisition but not retention. Behavioral observations showed that the control rats used a number of strategies during the process of problem solving that facilitated acquisition of the discrimination. Through modifications of training procedures, the processes of strategy selection and discrimination learning were dissociated. Cholinergic blockade was found to impair strategy selection but not discrimination learning. The results question the widely held view that cholinergic systems are involved in learning and memory and suggest instead that cholinergic systems are involved in the selection of the movements or strategies that are prerequisite for learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Chronic barbiturate treatment increases NMDA receptors but decreases kainate receptors in mouse cortex

Glycyrrhizin is the main component of glycyrrhiza. In this article an Ion-pair high performance liquid chromatography (HPLC) method is described for the determination of glycyrrhizin in two kinds of glycyrrhiza from different origins and twelve kinds of Chinese traditional patent medicine containing glycyrrhiza. A reversed phase system was used, including an ODS column with water and methanol (36:64) as the mobile phase which contained 5mmol/L tetra-n-butyl ammonium hydroxide and was adjusted to pH 6.0 by phosphoric acid. The column temperature was 35 degrees C; the detection was performed at 254 nm. Under this condition glycyrrhizin could be separated from other components. The limit of detection was 13ng, and the average recovery was 99.85%. During the experiments, we studied the concentration of counter-ion, the mixing ratio of methanol to water, the pH of the mobile phase and column temperature and their effect on the capacity factor of compound and resolution. We also studied the method of pre-treatment for the samples. The determination method is simple and accurate.     

Methamphetamine impairs sexual motivation but not sexual performance in male Japanese quail.

The present study investigated the effects of chronic pre-exposure to methamphetamine on sexual motivation and performance in male Japanese quail. Quail were pre-exposed to methamphetamine (1.0 or 3.0 mg/kg ip) or saline (ip) once daily for 10 days and locomotor activity was measured. After a 10 day washout period, sexual motivation was measured in a straight-arm runway with visual access to a female at one end. Three to 5 hr after sexual motivation tests, males were allowed to copulate with a receptive female quail and copulatory behavior was assessed. Tests were conducted once per day for 10 days. Results showed that males pre-exposed to methamphetamine had decreased locomotor activity compared to saline controls. Males pre-exposed to METH later ran slower toward a female in the runway and spent less time near her. In contrast, methamphetamine pre-exposed males showed similar copulatory behavior as saline pre-exposed males. The findings suggest that chronic pre-exposure to methamphetamine may impair sexual motivation but not sexual performance. The findings are discussed from a comparative perspective and with regard to their clinical relevance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Self-report measures of prospective memory are reliable but not valid.

Are self-report measures of prospective memory (ProM) reliable and valid? To examine this question, 240 undergraduate student volunteers completed several widely used self-report measures of ProM including the Prospective Memory Questionnaire (PMQ), the Prospective and Retrospective Memory Questionnaire (PRMQ), the Comprehensive Assessment of Prospective Memory (CAPM) questionnaire, self-reports of retrospective memory (RetM), objective measures of ProM and RetM, and measures of involvement in activities and events, memory strategies and aids use, personality and verbal intelligence. The results showed that both convergent and divergent validity of ProM self-reports are poor, even though we assessed ProM using a newly developed, reliable continuous measure. Further analyses showed that a substantial proportion of variability in ProM self-report scores was due to verbal intelligence, personality (conscientiousness, neuroticism), activities and event involvement (busyness), and use of memory strategies and aids. ProM self-reports have adequate reliability, but poor validity and should not be interpreted as reflecting ProM ability. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Involvement of hippocampal NMDA receptors in retention of shuttle avoidance conditioning in rats

The purpose of this research was to evaluate the role of hippocampal N-methyl-D-aspartate (NMDA) receptors in acquisition and consolidation of memory during shuttle avoidance conditioning in rats. Adult male Wistar rats were surgically implanted with cannulae aimed at the CA1 area of the dorsal hippocampus. After recovery from surgery, animals were trained and tested in a shuttle avoidance apparatus (30 trials, 0.5-mA footshock, 24-h training-test interval). Immediately before or immediately after training, animals received a bilateral intrahippocampal 0.5-microliter infusion containing 5.0 microgram of the NMDA competitive receptor antagonist aminophosphonopentanoic acid (AP5) or vehicle (phosphate-buffered saline, pH 7.4). Infusion duration was 2 min per side. Pre-training infusion of AP5 impaired retention test performance (mean +/- SEM number of conditioned responses (CRs) during retention test session was 16.47 +/- 1.78 in the vehicle group and 9.93 +/- 1.59 in the AP5 group; P < 0.05). Post-training infusion of AP5 did not affect retention (mean +/- SEM number of conditioned responses during retention test session was 18.46 +/- 1.94 in the vehicle group and 20.42 +/- 2.38 in the AP5 group; P > 0.10). This impairment could not be attributed to an effect on acquisition, motor activity or footshock sensitivity since AP5 affected neither training session performance measured by the number of CRs nor the number of intertrial crossings during the training session. These data suggest that NMDA receptors in the hippocampus are critical for retention of shuttle avoidance conditioning, in agreement with previous evidence showing a role of NMDA receptors in fear memory.     

Acute alcohol intoxication disrupts brightness but not olfactory conditioning in preweanling rats.

The present experiments tested the effect of acute alcohol administration on Pavlovian conditioning of 21-day-old rats using conditioned stimuli of two different sensory modalities—olfaction, an early developing sensory capacity functional at birth, and vision, a later developing sensory system not becoming functional until approximately 15 days of age. Conditioning and testing were conducted between 30 and 60 min following gastric intubation with either physiological saline or a mildly intoxicating alcohol dose (1.5 g/kg body weight). Brain alcohol levels were observed to remain at a peak and stable concentration during this period (Experiment 1). Alcohol impaired acquisition or expression of conditioned aversions to a visual cue paired with footshock when presented either as a single-element conditioned stimulus or as part of an odor/visual compound stimulus (Experiment 2), but it had no discernible effect on conditioned aversions to an olfactory stimulus that had similarly been paired with footshock (Experiments 2 and 3). The results suggest that alcohol may impair some aspects of learning but spare others, depending perhaps on the particular sensory modality to be conditioned. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Fimbria-Fornix lesions impair spatial working memory but not cognitive mapping.

Evaluated the relative merits of 2 theories of hippocampal function, the cognitive mapping theory, and the working memory theory. 49 albino male rats were tested in a series of maze tasks that varied in memory requirements. In Exps I and III, which required cognitive mapping but not working memory, Ss with fimbria–fornix lesions reached stable levels of performance that were as accurate as those of controls, and they also performed accurately during transfer tests, demonstrating that they used a cognitive mapping strategy to solve the discrimination. In Exp II, which required working memory, Ss with fimbria–fornix lesions performed at chance levels during all of postoperative testing, and they distributed their choices randomly between the correct and the incorrect goals. Results are consistent with the predictions of the working memory but not the cognitive mapping theory. Additional analyses examined the nature of a transitory impairment exhibited by Ss with fimbria–fornix lesions in 2 tasks that did not require working memory. Postoperatively, the performance of the Ss with lesions was initially impaired but recovered to normal levels with a time course similar to that seen during preoperative acquisition. Results require an extension of the working memory theory of hippocampal function, and discussion is focused on the possibility of a temporary retrograde amnesia following fimbria–fornix lesions and the distinctions between different types of memory abilities. (51 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)