Common humanity in the classroom: Increasing self-compassion and coping self-efficacy through a mindfulness-based intervention.

Objective To examine the effectiveness of a classroom-based mindfulness-based intervention (MBI) in improving stress, coping, and psychological well-being in college students. Participants: Sixty-one students at a small liberal arts college. Methods: As part of a college course, students in the MBI condition (N = 33) completed mindfulness meditations, reflective journaling, and participated in group discussions over the course of eight weeks. A control group of students (N = 28) received traditional instruction about stress and coping as part of a concurrently taught college course. Perceived stress, mental health, mindfulness, self-compassion, and coping self-efficacy were measured before and after the intervention and instruction. Results: Significant improvements in self-compassion and coping self-efficacy emerged, particularly in the domains of common humanity, isolation, and emotion-focused coping self-efficacy. Conclusions: These findings suggest that incorporation of MBIs into the classroom can be an effective strategy to enhance the well-being of college students.

Sensitization to the motor stimulant effects of 3,4-methylenedioxypyrovalerone (MDPV) and cross-sensitization to methamphetamine in rats.

BACKGROUND: In recent years, there has been a dramatic increase in abuse of the synthetic cathinone 3,4-methylenedioxypyrovalerone (MDPV), often in combination with other illicit stimulants. PURPOSE: We sought to determine if repeated exposure to MDPV would produce sensitization to the motor stimulant effects of the drug, and whether cross-sensitization would develop with the stimulant effects of methamphetamine (METH). STUDY DESIGN: Male Sprague-Dawley rats were administered MDPV (1 or 5 mg/kg) or saline once daily for 5 days at 24 hour intervals, or were administered MDPV (1 mg/kg) or saline once daily for 5 days at 48 hour intervals. For cross-sensitization experiments, rats were administered METH (1 mg/kg) or MDPV (1 or 5 mg/kg) once daily for 5 days at 48 hour intervals, and following a 5 day incubation period, were given an acute challenge injection of either MDPV (0.5 mg/kg) or METH (0.5 mg/kg), respectively. RESULTS: Rats repeatedly administered MDPV (1 mg/kg) every 48 hours, but not every 24 hours, demonstrated increased motor activity when given either a subsequent challenge of MDPV (0.5 mg/kg i.p.) or METH (0.5 mg/kg), indicating the development of behavioral sensitization and cross-sensitization, respectively. Moreover, rats repeatedly administered METH (1 mg/kg) every 48 hours did not exhibit cross-sensitization to the motor stimulating effects of a subsequent challenge with MDPV (0.5 mg/kg). CONCLUSION: These results suggest that specific patterns of MDPV administration may lead to lasting changes in behavioral responses to subsequent METH exposure.

mGluR5 Positive and Negative Allosteric Modulators Differentially Affect Dendritic Spine Density and Morphology in the Prefrontal Cortex.

Positive and negative allosteric modulators (PAMs and NAMs, respectively) of type 5 metabotropic glutamate receptors (mGluR5) are currently being investigated as novel treatments for neuropsychiatric diseases including drug addiction, schizophrenia, and Fragile X syndrome. However, only a handful of studies have examined the effects of mGluR5 PAMs or NAMs on the structural plasticity of dendritic spines in otherwise naïve animals, particularly in brain regions mediating executive function. In the present study, we assessed dendritic spine density and morphology in pyramidal cells of the medial prefrontal cortex (mPFC) after repeated administration of either the prototypical mGluR5 PAM 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5- yl)benzamide (CDPPB, 20 mg/kg), the clinically utilized mGluR5 NAM 1-(3-chlorophenyl)-3-(3-methyl-5-oxo-4Himidazol- 2-yl)urea (fenobam, 20 mg/kg), or vehicle in male Sprague-Dawley rats. Following once daily treatment for 10 consecutive days, coronal brain sections containing the mPFC underwent diolistic labeling and 3D image analysis of dendritic spines. Compared to vehicle treated animals, rats administered fenobam exhibited significant increases in dendritic spine density and the overall frequency of spines with small (<0.2 µm) head diameters, decreases in frequency of spines with medium (0.2-0.4 µm) head diameters, and had no changes in frequency of spines with large head diameters (>0.4 µm). Administration of CDPPB had no discernable effects on dendritic spine density or morphology, and neither CDPPB nor fenobam had any effect on spine length or volume. We conclude that mGluR5 PAMs and NAMs differentially affect mPFC dendritic spine structural plasticity in otherwise naïve animals, and additional studies assessing their effects in combination with cognitive or behavioral tasks are needed.

Sex-specific impairment and recovery of spatial learning following the end of chronic unpredictable restraint stress: potential relevance of limbic GAD.

Chronic restraint stress alters hippocampal-dependent spatial learning and memory in a sex-dependent manner, impairing spatial performance in male rats and leaving intact or facilitating performance in female rats. Moreover, these stress-induced spatial memory deficits improve following post-stress recovery in males. The current study examined whether restraint administered in an unpredictable manner would eliminate these sex differences and impact a post-stress period on spatial ability and limbic glutamic acid decarboxylase (GAD65) expression. Male (n=30) and female (n=30) adult Sprague-Dawley rats were assigned to non-stressed control (Con), chronic stress (Str-Imm), or chronic stress given a post-stress recovery period (Str-Rec). Stressed rats were unpredictably restrained for 21 days using daily non-repeated combinations of physical context, duration, and time of day. Then, all rats were tested on the radial arm water maze (RAWM) for 2 days and given one retention trial on the third day, with brains removed 30min later to assess GAD65 mRNA. In Str-Imm males, deficits occurred on day 1 of RAWM acquisition, an impairment that was not evident in the Str-Rec group. In contrast, females did not show significant outcomes following chronic stress or post-stress recovery. In males, amygdalar GAD65 expression negatively correlated with RAWM performance on day 1. In females, hippocampal CA1 GAD65 positively correlated with RAWM performance on day 1. These results demonstrate that GABAergic function may contribute to the sex differences observed following chronic stress. Furthermore, unpredictable restraint and a recovery period failed to eliminate the sex differences on spatial learning and memory.

mGluR5 positive allosteric modulation and its effects on MK-801 induced set-shifting impairments in a rat operant delayed matching/non-matching-to-sample task.

RATIONALE: Positive allosteric modulators (PAMs) of type 5 metabotropic glutamate receptors (mGluR5) exert pro-cognitive effects in animal models of various neuropsychiatric diseases. However, few studies to date have examined ability of mGluR5 PAMs to reverse cognitive deficits in operant delayed matching/non-matching-to-sample (DMS/DNMS) tasks. OBJECTIVES: This study aims to determine the ability of the mGluR5 PAM 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) to reverse set-shifting deficits induced by the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801. METHODS: Male Sprague-Dawley rats were initially trained to lever press for sucrose reinforcement under either DMS or DNMS conditions. Following successful acquisition of the task, reinforcement conditions were reversed (DNMS → DMS or DMS → DNMS). In Experiment 1, rats were treated daily prior to each session with vehicle/vehicle, vehicle/MK-801 (0.06 mg/kg) simultaneously, CDPPB (20 mg/kg)/MK-801 simultaneously, or CDPPB 30 min prior to MK-801. In Experiment 2, rats were treated with either vehicle/vehicle, vehicle/MK-801, or CDPPB 30 min prior to MK-801 only prior to sessions that followed task reversal. RESULTS: In Experiment 1, no group differences in initial task acquisition were observed. Rats treated with vehicle/MK-801 showed significant set-shifting impairments following task reversal, which were partially attenuated by simultaneous administration of CDPPB/MK-801 and completely precluded by administration of CDPPB 30 min prior to MK-801. In Experiment 2, MK-801 did not impair reversal learning, and no other group differences were observed. CONCLUSIONS: MK-801-induced deficits in operant set-shifting ability were prevented by pretreatment with CDPPB. MK-801 did not produce deficits in task learning when treatment was initiated following task reversal.

A novel role of the N terminus of budding yeast histone H3 variant Cse4 in ubiquitin-mediated proteolysis.

Regulating levels of centromeric histone H3 (CenH3) variant is crucial for genome stability. Interaction of Psh1, an E3 ligase, with the C terminus of Cse4 has been shown to contribute to its proteolysis. Here, we demonstrate a role for ubiquitination of the N terminus of Cse4 in regulating Cse4 proteolysis for faithful chromosome segregation and a role for Doa1 in ubiquitination of Cse4.

The neurocircuitry of illicit psychostimulant addiction: acute and chronic effects in humans.

Illicit psychostimulant addiction remains a significant problem worldwide, despite decades of research into the neural underpinnings and various treatment approaches. The purpose of this review is to provide a succinct overview of the neurocircuitry involved in drug addiction, as well as the acute and chronic effects of cocaine and amphetamines within this circuitry in humans. Investigational pharmacological treatments for illicit psychostimulant addiction are also reviewed. Our current knowledge base clearly demonstrates that illicit psychostimulants produce lasting adaptive neural and behavioral changes that contribute to the progression and maintenance of addiction. However, attempts at generating pharmacological treatments for psychostimulant addiction have historically focused on intervening at the level of the acute effects of these drugs. The lack of approved pharmacological treatments for psychostimulant addiction highlights the need for new treatment strategies, especially those that prevent or ameliorate the adaptive neural, cognitive, and behavioral changes caused by chronic use of this class of illicit drugs.

The involvement of Type II Neuregulin-1 in rat visuospatial learning and memory.

The cognitive deficits observed in schizophrenia are considered a core feature of the disease. Neuregulin-1 is a risk gene for schizophrenia that is involved in many neurodevelopmental and synaptic plasticity-related processes relevant to schizophrenia. Here, we have utilized a rat model (Nrg1(Tn)), which is hypomorphic for the neuregulin-1 (Nrg1) gene, to test whether reduced Type II NRG1 in the rat brain leads to cognitive deficits relevant to schizophrenia. Wild-type and homozygous Nrg1(Tn) male rats were tested in memory tasks that evaluated spatial memory (Morris water maze) and visuospatial working and reference memory (Can Test). Nrg1(Tn) rats were not impaired on the Morris water maze, but did show a deficit in the appetitive visuospatial discrimination test. Nrg1(Tn) rats committed more reference and working memory errors in this test. These results indicate that decreased Type II NRG1 in the brain may lead to deficits in visuospatial learning and memory.

Sex-specific neuroendocrine and behavioral phenotypes in hypomorphic Type II Neuregulin 1 rats.

Neuregulin 1 (NRG1) is an important growth factor involved in the development and plasticity of the central nervous system. Since its identification as a susceptibility gene for schizophrenia, several transgenic mouse models have been employed to elucidate the role NRG1 may play in the pathogenesis of psychiatric disease. Unfortunately very few studies have included females, despite the fact that some work suggests that the consequences of disrupted NRG1 expression may be sex-specific. Here, we used Nrg1 hypomorphic (Nrg1(Tn)) Fischer rats to demonstrate sex-specific changes in neuroendocrine and behavioral phenotypes as a consequence of reduced Type II NRG1 expression. We have previously shown that male Nrg1(Tn) rats have increased basal corticosterone levels, and fail to habituate to an open field despite normal overall levels of locomotor activity. The current studies show that, in contrast, female Nrg1(Tn) rats exhibit enhanced suppression of corticosterone levels following an acute stress, reduced locomotor activity, and enhanced habituation to novel environments. Furthermore, we also show that female, but not male, Nrg1(Tn) rats have impaired prepulse inhibition. Finally, we provide evidence that sex-specific changes are not likely attributable to major disruptions in the hypothalamic-pituitary-gonadal axis, as measures of pubertal onset, estrous cyclicity, and reproductive capacity were unaltered in female Nrg1(Tn) rats. Our results provide further support for both the involvement of NRG1 in the control of hypothalamic-pituitary-adrenal axis function and the sex-specific nature of this relationship.

Characterization of the cognitive impairments induced by prenatal exposure to stress in the rat.

We have previously shown that male rats exposed to gestational stress exhibit phenotypes resembling what is observed in schizophrenia, including hypersensitivity to amphetamine, blunted sensory gating, disrupted social behavior, impaired stress axis regulation, and aberrant prefrontal expression of genes involved in synaptic plasticity. Maternal psychological stress during pregnancy has been associated with adverse cognitive outcomes among children, as well as an increased risk for developing schizophrenia, which is characterized by significant cognitive deficits. We sought to characterize the long-term cognitive outcome of prenatal stress using a preclinical paradigm, which is readily amenable to the development of novel therapeutic strategies. Rats exposed to repeated variable prenatal stress during the third week of gestation were evaluated using a battery of cognitive tests, including the novel object recognition task, cued and contextual fear conditioning, the Morris water maze, and iterative versions of a paradigm in which working and reference memory for both objects and spatial locations can be assessed (the "Can Test"). Prenatally stressed males were impaired relative to controls on each of these tasks, confirming the face validity of this preclinical paradigm and extending the cognitive implications of prenatal stress exposure beyond the hippocampus. Interestingly, in experiments where both sexes were included, the performance of females was found to be less affected by prenatal stress compared to that of males. This could be related to the finding that women are less vulnerable than men to schizophrenia, and merits further investigation.

Biomechanical comparison of facet-sparing laminectomy and Christmas tree laminectomy.

OBJECT: The authors compared differences in biomechanical stability between two decompressive laminectomy techniques for treating lumbar stenosis. A Christmas tree laminectomy (CTL), in which bilateral facetectomies and foraminotomies are performed, was compared with facet-sparing laminectomy (FSL), in which the facets are undercut but not resected. Spinal instability was assessed immediately postoperatively and again after discectomy to model long-term degeneration. METHODS: Sixteen motion segments obtained from five human cadaveric lumbar specimens were studied in vitro by conducting nondestructive flexibility tests. Specimens were tested intact, after FSL or CTL, and again after discectomy. Nonconstraining torques (< or = 5 Nm) were applied to induce flexion, extension, axial rotation, and lateral bending; strings and pulleys were used while vertebral angles were measured. Anteroposterior translation in response to shear loading (< or = 100 N) was also measured. Angular motion, shear motion, and sagittal-plane axes of rotation were compared to evaluate stability. Compared with the intact condition, CTL-treated specimens had significantly larger increases in angular motion during flexion, lateral bending, and axial rotation than their FSL-treated counterparts (p < 0.05, nonpaired Student t-tests). Subsequent discectomy caused greater increases in motion in the CTL group. Axes of rotation shifted less from their normal positions after FSL than after CTL. CONCLUSIONS: This study provides objective evidence that the treatment of lumbar stenosis with FSL induces less biomechanical instability and alters kinematics less than FSL. These findings support the use of the FSL in treating lumbar stenosis.