Effects of intraseptal zolpidem and chlordiazepoxide on spatial working memory and high-affinity choline uptake in the hippocampus

Injection of GABA(A)/benzodiazepine receptor ligands into the medial septum (MS) alters the activity of cholinergic neurons that innervate the hippocampus and can produce bidirectional modulation of spatial memory. Recent evidence suggests that two subtypes of the GABA(A) receptor are differentially localized to either GABAergic (alpha(1)/beta(2)/gamma(2)) or cholinergic (alpha(3)/beta(3)/gamma(2)) neurons within the MS. The present studies characterized the dose-related behavioral and neurochemical effects of intraseptal infusions of two benzodiazepine (BDZ) agonists that appear to exhibit different profiles of pharmacological specificity for these receptor subtypes. Male Sprague-Dawley rats were cannulated and then artificial CSF, chlordiazepoxide (CDP: 8 or 12 microg), or zolpidem (4, 8, or 12 microg) was injected into the MS. Spatial working memory was assessed in a delay radial-arm maze task and the activity of cholinergic neurons in the MS was evaluated by high-affinity choline uptake (HA-ChU) in the hippocampus. Intraseptal injection of either CDP or zolpidem produced dose-related impairments in spatial working memory and decreases in hippocampal HAChU. Both BDZ agonists were found to produce retrograde memory deficits and a decrease in HAChU following the highest dose tested (12 microg). However, intraseptal injection of 8 microg of zolpidem produced a behavioral deficit comparable to the high dose of CDP, but did not alter HAChU within the HPC. Although the cholinergic component of the septohippocampal pathway has been shown to be important in modulating hippocampal physiology and spatial memory processes, data from the present experiments suggest that the GABAergic component may also play an important role in the behavioral functions of the septohippocampal pathway.     

Validation of Iranian Version of FI-QOL Scale in Patients with Fecal Incontinence

Pelvic floor dysfunction is a general public health problem with great impact on quality of life. Inability to control the passage of stool can produce embarrassment and may limit daily activities. One of the most important indicators of effectiveness of therapy in patients with fecal incontinence (FI) can be patient’s quality of life. Therefore, a well-constructed questionnaires studying quality of life is necessary. The objective of this study was to assess the Iranian version of Fecal Incontinence Quality of Life Scale in a hospital-based study on patients with FI. Two hundred women were recruited in the study. One group included patients with FI (n = 100) and the control group (n = 100) included patients with any gastrointestinal (GI) problems except FI. The Persian version of fecal incontinence quality of life scale completed by two groups. The FI patients completed the SF-36 questionnaire too. Reliability and validity of questionnaire were evaluated by Cronbach’s alpha, test/retest using correlation analysis, Intraclass correlation coefficient, paired t-test, and analysis of variance. There was not any significant differences between two groups for age, marital status, education, and occupation. The mean age of FI patients and controls were 42.6 (±13.3) and 44.5 (±15.0) respectively. Cronbach’s-α for all domains ranged between 0.72 and 0.92. All scales showed significant correlation between the test and retest administration of questionnaire. The FI patients had lower scores than the controls for all domains adjusted for gender. All correlations between six selected domains of Sf-36 scales and FIQL scales were significant at P ≤ 0.05 levels. The Persian version of FIQL had a good validity and reliability and can be used for accurate measure of quality of life in FI patients.     

Hippocampal theta (3-8Hz) activity during classical eyeblink conditioning in rabbits

In 1978, Berry and Thompson showed that the amount of theta (3–8 Hz) activity in the spontaneous hippocampal EEG predicted learning rate in subsequent eyeblink conditioning in rabbits. More recently, the absence of theta activity during the training trial has been shown to have a detrimental effect on learning rate. Here, we aimed to further explore the relationship between theta activity and classical eyeblink conditioning by determining how the relative power of hippocampal theta activity [theta/(theta + delta) ratio] changes during both unpaired control and paired training phases. We found that animals with a higher hippocampal theta ratio immediately before conditioning learned faster and also that in these animals the theta ratio was higher throughout both experimental phases. In fact, while the hippocampal theta ratio remained stable in the fast learners as a function of training, it decreased in the slow learners already during unpaired training. In addition, the presence of hippocampal theta activity enhanced the hippocampal model of the conditioned response (CR) and seemed to be beneficial for CR performance in terms of peak latency during conditioning, but did not have any effect when the animals showed asymptotic learning. Together with earlier findings, these results imply that the behavioral state in which hippocampal theta activity is absent is detrimental for learning, and that the behavioral state in which hippocampal theta activity dominates is beneficial for learning, at least before a well-learned state is achieved.     

Distinct Profile of Working Memory Errors Following Acute or Chronic Disruption of the Cholinergic Septohippocampal Pathway

The behavioral effects of two amnestic treatments (intraseptal chlordiazepoxide (CDP) and intraventricular AF64A) were examined in a delayed-nonmatch-to-sample radial-arm maze (DNMTS) paradigm. The types of errors induced by these treatments in this working memory task were assessed to determine how acute and chronic disruptions of the medial septum affect different phases of working memory (encoding, maintenance, retrieval). Rats were initially trained to perform the DNMTS task with a 1-h delay imposed between the training and the testing sessions. The first experiment demonstrated that intraseptal injection of 30 nmoles of CDP did not produce state-dependent learning. Rats were injected immediately following training with CDP or artificial cerobrospinal fluid (CSF; drug vehicle) and then prior to testing with CDP or CSF. Injection of CDP immediately following training (CDP–CSF) impaired performance of the task regardless of whether CDP was also administered before the postdelay test (CDP–CDP). Rats infused with CDP only before the postdelay test (CSF–CDP) exhibited a proactive deficit characterized by intact retention of the predelay information (i.e., arms entered prior to the delay) but impaired performance on the postdelay component (arms entered only after the delay). These data indicate: (i) that state dependency does not explain the working memory deficits induced by intraseptal CDP; (ii) that pretest CDP disrupts the storage and utilization of working memory for current arm selections. The second experiment examined the behavioral effects induced by a permanent disruption of the cholinergic septohippocampal pathway produced by icv injection of the cholinotoxin AF64A. Rats were initially trained on the DNMTS task and then bilaterally injected icv with either AF64A (2.5 nmoles/side) or CSF. AF64A-treated rats exhibited a significant impairment of performance compared to CSF-treated controls. In contrast to the impairment exhibited by CDP-treated rats in Experiment 1, the performance of AF64A-treated rats displayed a deficit in the maintenance/retrieval of information acquired during RAM trainingandan impairment in ability to store current spatial information in working memory to guide postdelay testing performance. These studies demonstrate that acute and chronic disruptions of the septohippocampal pathway produce distinct profiles of cognitive impairment that should help to reveal the behavioral and neurobiological characteristics of spatial memory.     

Rate-dependent effect of methylphenidate(Ritalin) on fixed-interval behavior in rats

The behavioral effects of 1.0–18.0 mg/kg methylphenidate (Ritalin) injections on leverpressing reinforced under a fixed-interval (FI) 60-sec schedule for water in Mäll-Wistar rats were studied. Effets of methylphenidate were dose-dependent: it increased response rates early in the FI 60-sec adn reduced the higher response rates later in the FI, without changing the average response rate. There was no systematic effect of the drug upon locomotor activity. The local response-rate change during the FI 60-sec are in accord with the rate-dependency hypothesis (Dews, 1958). the bidirectional response-rate changes withing the FI explain why methylphenidate did not affect the average response rate.     

The GABAergic effect of low doses of lorazepam on social behavior

The aim of this work was to test the antiaggressive effects of lorazepam and to determine whether these effects were mediated by benzodiazepine receptors. In a first experiment, male mice were injected with lorazepam in a range of low doses (0.05, 0.1, 0.2, and 0.6 mg/kg) or saline solution. In a second experiment, 1 mg/kg of Ro 15‐1788, a benzodiazepine receptor antagonist, and a saline solution were injected before the behavioral test. Results showed that 0.6 mg/kg of lorazepam was the only dose that decreased the total duration of threat (P < .01) and social investigation (P < .05) and that 1 mg/kg of Ro 15‐1788 had no effects. In the third experiment, animals received two injections: 0.6 mg/kg of lorazepam plus 1 mg/kg of Ro 15‐1788, 0.6 mg/kg of lorazepam plus saline solution, or saline solution plus saline solution. Those treated with lorazepam and saline solution spent less time digging (P < .001), threatening (P < .001), and attacking (P < .05) and more time avoiding the opponent (P < .01) or being immobile (P < .001) than the controls. Ro 15‐1788 was successful in completely antagonizing the behavior modulated by lorazepam. Aggr. Behav. 28:248–256, 2002. © 2002 Wiley‐Liss, Inc.     

Test of a Factor Mixture-Based Taxonic-Dimensional Model of Anxiety Sensitivity and Panic Attack Vulnerability among University and Clinical Samples in Mexico City

The aim of the present study was to evaluate a factor mixture-based taxonic-dimensional model of anxiety sensitivity (AS) (Bernstein et al. Behavior Therapy 41:515-521, 2010), as measured by the ASI-3 (Taylor et al. Psychological Assessment 19:176-188, 2007), in regard to panic attacks, anxiety symptoms, and behavioral impairment among a university sample (N = 150, n _females  = 107, M _age = 21.3 years, SD = 4.3) and a clinical sample (N = 150, n _females  = 102, M _age = 39.0 years, SD = 12.0) from Mexico City, Mexico. Findings demonstrated cross-national support for the conceptual and operational utility of the AS taxonic-dimensional hypothesis (Bernstein et al. Journal of Anxiety Disorders 20:1-22, 2007b). Specifically, (1) the FMM-based AS taxon class base rate was significantly greater among the clinical relative to the university sample; (2) risk for panic attacks was significantly greater among the AS taxon class relative to the AS normative class; and (3) continuous individual differences in AS physical and psychological concerns, within the AS taxon class, were associated with level of risk for panic attacks, as well as panic attack severity and anxiety symptom levels. Similar AS taxonic-dimensional effects were observed in relation to degree of behavioral impairment across domains of functioning. The study results are discussed with respect to their implications for better understanding the nature of AS-related cognitive vulnerability for panic and related anxiety psychopathology.     

Multiple fixed-interval schedules: transient contrast and temporal inhibition

Pigeons were exposed to four cycles per session of a multiple schedule in which each cycle involved twelve 60-sec fixed intervals followed by four 180-sec intervals [(12 FI 60-sec)(4 FI 180-sec) schedule]. Post-reinforcement pauses were shorter during the first few short intervals of each cycle than during later short intervals, and increased over the four long intervals of each cycle (positive and negative transient contrast). A (12 FI 15-sec)(4 FI 45-sec) schedule showed similar results. These two schedules differed in some other respects indicating effects of absolute FI duration on stimulus control. Differences in contrast properties between both these procedures and multiple variable-interval schedules were related to the pause-producing property of reinforcement on FI (temporal inhibition). Behavior under two other multiple fixed-interval schedules—(2 FI 360-sec)(1 FI 720-sec) and (3 FI 360-sec)(1 FI 720-sec)—differed in certain respects from both the (12 FI x-sec)(4 FI 3x-sec) schedules. These differences may be related to differences in the number of successive fixed intervals within a component (run length).     

Rostral anterior cingulate activity generates posterior versus anterior theta activity linked to agentic extraversion

Recent research using the resting electroencephalogram (EEG) showed that posterior versus anterior theta activity (around 4–8 Hz) is consistently associated with agency, reflecting the dopaminergic core of extraversion (i.e., incentive motivation, positive emotion). Neuroimaging studies using various methodologies and experimental paradigms have converged on the anterior cingulate cortex (ACC) as a neurophysiological correlate of extraversion. The aim of the present study is integrate these lines of research by testing the hypothesis that posterior versus anterior EEG theta is at least partly based on ACC theta activity. Resting EEG data were analyzed in N = 78 healthy, male participants extremely high or low in agentic extraversion (aE). Using the low-resolution electromagnetic tomography algorithm, we localized the sources of aE-dependent intracerebral theta activity within rostral subdivisions of the ACC. The posterior versus anterior index and theta current density within the rostral ACC were significantly correlated (r = -.52), and both displayed high retest stability across 5 hr and were associated with traits from the aE spectrum. These neurophysiological correlates of aE and their possible functional significance are discussed.     

Consensual and behavioral validity of a measure of adaptive individual differences dimensions in human motivation

Data from three sources—an initial self sample (N = 108) and a friend sample (N = 103) and relative sample (N = 103) recruited by self sample participants—were used to test the consensual and behavioral validity of new individual differences measures of 15 dimensions of motivation represented in the assessment of individual motives-questionnaire (AIM-Q). AIM-Q scores for all three samples converged and hypotheses of their predicted relationships with reports of the occurrence and frequency of a variety of behavior criteria of some importance were supported in most cases. These results support the utility of the AIM-Q as a new measure of motives in purposeful human behavior.     

The Impact of Fallible Item Parameter Estimates on Latent Trait Recovery

In this paper we propose an upward correction to the standard error (SE) estimation of [^(q)]_ML\hat{\theta}_{\mathrm{ML}} , the maximum likelihood (ML) estimate of the latent trait in item response theory (IRT). More specifically, the upward correction is provided for the SE of [^(q)]_ML\hat{\theta}_{\mathrm{ML}} when item parameter estimates obtained from an independent pretest sample are used in IRT scoring. When item parameter estimates are employed, the resulting latent trait estimate is called pseudo maximum likelihood (PML) estimate. Traditionally, the SE of [^(q)]_ML\hat{\theta}_{\mathrm{ML}} is obtained on the basis of test information only, as if the item parameters are known. The upward correction takes into account the error that is carried over from the estimation of item parameters, in addition to the error in latent trait recovery itself. Our simulation study shows that both types of SE estimates are very good when θ is in the middle range of the latent trait distribution, but the upward-corrected SEs are more accurate than the traditional ones when θ takes more extreme values.     

Moving beyond Coltheart’s <Emphasis Type="Italic">N</Emphasis>: A new measure of orthographic similarity

Visual word recognition studies commonly measure the orthographic similarity of words using Coltheart’s orthographic neighborhood size metric (ON). Although ON reliably predicts behavioral variability in many lexical tasks, its utility is inherently limited by its relatively restrictive definition. In the present article, we introduce a new measure of orthographic similarity generated using a standard computer science metric of string similarity (Levenshtein distance). Unlike ON, the new measure—named orthographic Levenshtein distance 20 (OLD20)—incorporates comparisons between all pairs of words in the lexicon, including words of different lengths. We demonstrate that OLD20 provides significant advantages over ON in predicting both lexical decision and pronunciation performance in three large data sets. Moreover, OLD20 interacts more strongly with word frequency and shows stronger effects of neighborhood frequency than does ON. The discussion section focuses on the implications of these results for models of visual word recognition.     

Hippocampal Theta Oscillations and Classical Conditioning

Studies are reviewed that support a hypothesized role for hippocampal theta oscillations in the neural plasticity underlying behavioral learning. Begun in Richard F. Thompson's laboratory in the 1970s, these experiments have documented a relationship between free-running 3- to 7-Hz hippocampal slow waves (theta) and rates of acquisition in rabbit classical nictitating membrane (NM) conditioning. Lesion and drug manipulations of septohippocampal projections have affected NM and jaw movement conditioning in ways consistent with a theta-related brain state being an important modulator of behavioral acquisition. These findings provide essential empirical support for the recently developed neurobiological and computational models that posit an important role for rhythmic oscillations (such as theta) in cellular plasticity and behavioral learning.     

Individual differences in intuitive processing moderate responses to moral transgressions

Despite the widespread recognition that intuitive processing is integral to moral judgment, research has provided minimal support for the role of individual differences in faith in intuition (FI) in moral outcomes. We propose that reliance on intuitive processing is likely to influence moral behavior when people experience internally generated morally-relevant feelings. We conducted two studies to test this proposal, examining whether FI would moderate the effects of moral recall manipulations on morally-relevant outcomes. In Study 1 (N = 120), FI moderated the effects of condition such that after imagining telling a lie in an email, people high in FI gave increased valuations of hand cleansing products. In Study 2 (N = 197), FI moderated the effects of condition such that after recalling a past personally relevant immoral act, FI predicted less cheating on an unsolvable IQ test. Implications for moral psychology and the importance of theoretically informed methods for studying the role of individual differences in intuitive processing are discussed.     

Proactive behavioral effects of theta-blocking septal stimulation in the rat

The induction of hippocampal theta rhythm using low-frequency septal stimulation has been shown to proactively (1) facilitate the acquisition and (2) increase resistance to extinction of a food-rewarded fixed-ratio (FR) bar-press response (Holt & Gray, Quarterly Journal of Experimental Psychology, 35B, 97-118, 1983). Both (1) and (2) are also seen after septal lesions. This suggests that Holt and Gray's (1983) results may have been due either to stimulation-produced theta waves (the "theta" hypothesis), or a small septal lesion produced by the stimulating current (the "lesion" hypothesis). Both hypotheses were tested in the present experiment using high-frequency septal stimulation. In one of two treatment conditions male Sprague-Dawley rats, chronically implanted with a bilateral septal stimulating electrode and a unilateral bipolar hippocampal recording electrode, received (1) trains of continuous pulses at 77 Hz which blocked the hippocampal theta rhythm, or (2) trains of pulses at 100 Hz interrupted by a 30-msec interval at a frequency of 7.7 Hz. Control animals were implanted but not stimulated. Acquisition of a discrete-trial bar-press response on a fixed ratio 5 reinforcement schedule immediately followed the treatment phase. After 15 days' acquisition all animals were extinguished over the subsequent 12 days. Results indicated that both types of septal stimulation reduced resistance to extinction of barpressing; theta-blocking stimulation produced the greater effect. Theta-blocking stimulation retarded the acquisition of bar-pressing in the early stages of training. These overall results are exactly opposite to those produced by low-frequency (7.7 Hz) theta-driving septal stimulation (Holt & Gray, 1983) and contrary to the predictions of the lesion hypothesis. Furthermore, these findings support the idea that long-term changes in behavior may depend on stimulation-produced changes in the hippocampal theta rhythm.     

Effects of moderate chronic ethanol consumption on hippocampal nicotinic receptors and associative learning

A number of studies have reported that ethanol exposure induces changes in different brain systems. The hippocampus is a brain region that is very vulnerable to ethanol exposition, which functionally results in impairment of learning and memory processes reported in heavy drinkers. Hippocampal nicotinic receptors are involved in learning and memory. In this study, we determined the effects of ethanol on the main hippocampal subtypes of neural nicotinic receptors (α7 and α4β2) in rats non-selected for alcohol consumption, in order to check for possible changes on these receptors that could be linked with alterations in learning acquisition. Binding assays were carried out with [³H]methyllycaconitine ([³H]MLA) to study the α7 and [³H]nicotine to study α4β2 receptors. Auto-shaping, continuous ratio and extinction procedures were used as behavioral tests. The results show that moderate chronic ethanol consumption for 10 weeks produces: (a) a decrease of both hippocampal nicotinic receptor subtypes without alterations in affinity; (b) no differences in behavioral performance between control rats and ethanol-drinking rats in auto-shaping and continuous ratio; (c) an improvement of performance of extinction paradigm. These results indicate that chronic ethanol consumption, at moderate levels, induces changes in hippocampal nicotinic receptors but does not impair acquisition and performance of new associative learning and even improves some kind of paradigms. These results may have implications in the biochemical basis of interactions between alcohol and nicotine and the effects of these drugs on behavior.     

Inhibiting progesterone metabolism in the hippocampus of rats in behavioral estrus decreases anxiolytic behaviors and enhances exploratory and antinociceptive behaviors

Blocking progesterone’s metabolism to 5α -pregnan-3α -ol-20-one (3α ,5α -THP) with finasteride, a 5α -reductase inhibitor, and effects on anxiolytic, exploratory, and antinociceptive behaviors of rats in behavioral estrus were examined. Rats in behavioral estrus received finasteride systemically (SC), to the hippocampus, or to control implant sites, the nucleus accumbens (NA) or ventral tegmental area (VTA), and were tested in horizontal crossing, open-field, elevated plus-maze, emergence, holeboard, social interaction, tailflick, pawlick, and defensive freezing tasks. Finasteride, SC or intrahippocampally, reduced 3α ,5α -THP in the hippocampus relative to vehicle implants or finasteride to the NA or VTA. Systemic or intrahippocampal finasteride decreased central entries in the open field and open-arm time on the elevated plus-maze and increased freezing in response to shock relative to vehicle. Finasteride to the hippocampus decreased emergence latencies and increased social interaction, pawlick, and tailflick latencies relative to all other groups. Finasteride to the hippocampus of rats in behavioral estrous decreased anxiolysis and enhanced exploration and analgesia. In summary, these data demonstrate that decreases in anxiolytic behavior of behavioral estrous rats can be produced by reductions in 3α ,5α -THP in the hippocampus, which suggest that elevations in 3α ,5α -THP in the hippocampus may give rise to anxiolysis seen during behavioral estrus.     

The Starting Early Starting Smart Integrated Services Model: Improving Access to Behavioral Health Services in the Pediatric Health Care Setting for At-Risk Families with Young Children

We evaluated the Starting Early Starting Smart (SESS) national initiative to integrate behavioral health services (parenting, mental health, and drug treatment) into the pediatric health care setting for families with young children. Data are presented from five pediatric care (PC) sites, drawing from families at risk due to demographic and behavioral health factors, with infants less than 12 months of age (n = 612). Families were randomly assigned to either the SESS program or a standard care Comparison group. We utilized longitudinal analyses to estimate differences in utilization rates for parenting, mental health, and drug treatment over 6 follow-up time points (3, 6, 9, 12, 15 and 18 months). Our findings indicate that SESS caregiver participants were 4.6 times (p < 0.001; CI = 3.33–6.26) more likely to receive parenting services, 2.1 times (p < 0.001; CI = 1.48–2.86) more likely to receive outpatient mental health treatment, and 1.8 times (p = 0.025; CI = 1.08–3.14) more likely to receive drug treatment than Comparison group participants. Our results demonstrate the success of the SESS program in coordinating and improving access to behavioral health services for high-risk caregivers within the pediatric health care setting and highlight the importance of continuing to focus public health policy on the behavioral health care needs of families with young children.     

The effect of multiple SΔ periods on responding on a fixed-interval schedule

The effect of repeated interruption of FI responding by short S^Δ presentations on the pattern of increasing frequency of responding through the interval has been studied. Although the S^Δ profoundly changed the pattern of responding during their presentation, the general scalloped pattern of FI responding survived. The implication of these findings for understanding the role of chaining of responses in FI patterns is discussed. It is suggested that chaining is not a necessary condition for the scalloped pattern.