Poppy Seed Consumption and Oral Fluid Opioids Detection: A Classroom Demonstration of Psychopharmacological Concepts.

Psychopharmacological concepts such as pharmacokinetics, pharmacodynamics and drug interactions can be difficult to illustrate within the college classroom. In this demonstration, students consume poppy seed-containing food items, assess opioid content in their oral fluid using commercial drug test kits, and relate the findings to learned materials, its real-life applications, and relevant societal implications. This demonstration can clarify processes such as drug absorption, distribution, metabolism, and excretion (ADME), broaden the review of information relevant to opioids mechanisms of action, and facilitate the discussion of topics such as drug abuse, dependence, and addiction, as well as drug development, testing, policy, and enforcement. Instructors can employ different experimental designs, create dose-dependent/timeline detection plots, or allow students to construct their own experiments, assessing possible mediators of opioid detection. The demonstration can also be utilized to discuss scientific myths, truths, data misinterpretation and misrepresentation. Several optional protocols are provided, required materials are indicated, and discussion points are suggested.

Neuroscience Ambassadors: Creating a Network of Academia-CommunityPartnerships.

The field of neuroscience offers exciting, yet complex, insights into the human mind. In recent years, the need to improve the dialogue between neuroscientists and the public has been recognized, and an emphasis has been placed on the generation of public-based educational programs which reach outside the academic environment and into the community. One promising avenue includes the generation of mutually beneficial academia-community partnerships. These have the potential to allow faculty and students to acquire the necessary skills to become effective "neuroscience ambassadors", while delivering attractive, fun, informative and educational opportunities to the general public. The Department of Psychology/Interdisciplinary Neuroscience Minor at Saint Francis University (SFU) created a public-oriented, neuroscience-based network of educational programs with local public libraries, Girl and Cub scout troops, elementary schools, high schools, children museums and nursing homes, in rural Pennsylvania. We envisioned that the programs will serve to improve academia-community conversations and benefit students, faculty, community partners and the public alike. In this paper, the design, implementation, implications, limitations, and future directions of the project are discussed.

Mood-stabilizing effects of rapamycin and its analog temsirolimus: relevance to autophagy.

Accumulated data support a relationship between mood disorders and cellular plasticity and resilience, some suggesting relevance to autophagy. Our previous data show that pharmacological enhancement of autophagy results in antidepressant-like effects in mice. The current study was designed to further examine the effects of autophagy enhancement on mood by testing the effects of subchronic treatment with the mammalian target of rapamycin (mTOR) inhibitors and autophagy enhancers rapamycin and temsirolimus in a model for mania and in a model for antidepressant action, respectively. The results show that rapamycin reduced mania-like aggression and reward-seeking behaviors, with no effects on locomotion. Temsirolimus reduced depression-related immobility in the forced-swim test without effects on locomotion in the open field or on anxiety-related measures in the elevated plus maze. Taken together with our previous findings, these data support the notion that enhancing autophagy may have mood-stabilizing effects.

Stress-induced epigenetic regulation of κ-opioid receptor gene involves transcription factor c-Myc.

Exposure to stress is associated with adverse emotional and behavioral responses. Whereas the κ-opioid receptor (KOR) system is known to mediate some of the effects, it is unclear whether and how stress affects epigenetic regulation of this gene. Because the KOR gene can use two promoters (Pr1 and Pr2) and two polyadenylation signals (PA1 and PA2), it is also interesting whether and how these distinct regulatory mechanisms are differentially modulated by stress. The current study examined the effects of stress on these different regulatory mechanisms of the KOR gene. Results showed that stress selectively increased the expression of KOR mRNA isoforms controlled by Pr1 and terminated at PA1 in specific brain areas including the medial-prefrontal cortex, hippocampus, brainstem, and sensorimotor cortex, but not in the amygdala or hypothalamus. These effects correlated with altered epigenetic state of KOR Pr1 chromatin, as well as elevation and increased recruitment of the principal transcription factor c-Myc, which could activate Pr1. Stress-induced modulation of Pr1 was further validated using glutamate-sensitive murine hippocampal cell line, HT22. The results revealed a common molecular mechanism underlying the effect of stress on selected chromatin regions of this gene at the cellular level and in the context of whole animal and identified a critical role for c-Myc in stress-triggered epigenetic regulation of the KOR gene locus. This study sheds light on the mechanisms of stress-induced epigenetic regulation that targets specific chromatin segments and suggests certain KOR transcripts and its principal transcription factor c-Myc as potential targets for brain-area-specific intervention.

Inconsistent effects of photoperiod manipulations in tests for affective-like changes in mice: implications for the selection of appropriate model animals.

Deficiencies in appropriate animal models are a significant factor hindering the research of affective disorders. Significant data suggest that systems related to circadian rhythms are strongly linked to affective changes, but study with animal models in this context had unclear and inconsistent results. Circadian physiology is significantly different in diurnal and nocturnal animals and a recent project showed that in diurnal rodents, short photoperiods induce depression and anxiety-like phenotypes. This study was designed to evaluate the possibility that using a similar methodology would also result in behavioral changes in nocturnal mice. Mice from two strains were maintained in either short photoperiod, neutral photoperiod or long photoperiod for 3 weeks and tested for depression or anxiety-related behaviors, as done earlier with the diurnal rodents. Tests included activity levels, sweet solution preference, elevated plus-maze, resident-intruder aggression, and forced swim test. Tests were conducted either during the light phase or during the dark phase of the mice. In contrast to the clear phenotype in diurnal rodents, the effects of photoperiod manipulations in nocturnal mice were inconsistent. These results suggest that diurnal rodents may be advantageous compared with nocturnal species for studies exploring the relationship between circadian rhythms and affective disorders.

Old Dogs Can Learn New Tricks: Using the Academic Classroom to Improve the Adoption Outcomes of 10 Shelter Dogs.

Animal shelters around the US are commonly overpopulated, and canine-specific behavioral rehabilitation opportunities within shelters are limited. The current project explored the possibility of integrating a canine-training program into the academic undergraduate Psychology curriculum. Students enrolled in the "Canine Learning and Behavior" class at Saint Francis University fostered and trained a total of 10 shelter dogs throughout three academic semesters, and the effectiveness of the program on the behavior of the dogs was evaluated. Findings demonstrated that the behavioral repertoire of all trained dogs improved, as assessed using a 10-item questionnaire tailored to the American Kennel Club "Canine Good Citizen" (AKC-CGC) test. Results also demonstrated that most dogs passed the AKC-CGC test conducted by a certified evaluator, and that all dogs were successfully adopted into their forever homes. The implications, limitations, and future directions of the study are discussed.

Proposing the sweet solution preference test as a screening assay for anti-manic effects of mood stabilizers.

BACKGROUND: There is a desperate need for in-vivo behavioral screening tests for anti-manic effects. The frequently used psychostimulant-induced hyperactivity test appears to have lower validity than previously described, but other quick, simple and high throughput tests are currently unavailable. NEW METHOD: In the context of modeling the behavioral facets of mania, we previously suggested that the sweet solution preference test (SSP) in naive mice might have predictive validity for screening anti-manic effects. The current study further examined this proposal by testing the effects of lithium, valproate and imipramine on SSP in three strains of mice (male mice from the black Swiss, ICR and C57bl/6 strains) and an exploratory test in females (black Swiss strain). RESULTS: Data demonstrate that lithium and valproate at appropriate dosing schedules significantly and reliably reduce SSP in all three strains (including in females) but that the antidepressant imipramine has no effects. COMPARISON WITH EXISTING METHODS: The results support the utilization of the SSP as mice screening model for anti-manic effects of drugs with stronger predictive validity compared with other methods. CONCLUSIONS: The SSP is not a comprehensive model for bipolar disorder but it has good predictive validity and strong practical value that can be applied towards simple and fast screening of large numbers of animals, without the need for specialized equipment or complicated/prolonged procedures. We therefore propose that the SSP is an advantageous screening assay for testing novel mood stabilizing drugs for anti-manic properties.

Ovarian hormones modulate 'compulsive' lever-pressing in female rats.

Life events related to the female hormonal cycle may trigger the onset of obsessive-compulsive disorder (OCD) or exacerbate symptoms in women already suffering from it. These observations suggest a possible role for ovarian hormones in the course of this disorder. Yet, the mechanisms that may subserve the modulatory effect of ovarian hormones are currently unknown. The aim of the present study was therefore to test the role of ovarian hormones in the signal attenuation rat model of OCD. Experiment 1 compared the behavior of pre-pubertal and adult male and female rats in the model, and found no age and sex differences in compulsive responding. Experiment 2 found that compulsive responding fluctuates along the estrous cycle, being highest during late diestrous and lowest during estrous. Acute administration of estradiol to pre-pubertal female rats was found to attenuate compulsive behavior (Experiment 3), and withdrawal from chronic administration of estradiol was shown to increase this behavior (Experiment 4). These findings extend the use of the signal attenuation model of OCD to female rats, and by demonstrating that the model is sensitive to the levels of ovarian hormones, provide the basis for using the model to study the role of ovarian hormones in OCD. In addition, the present findings support the hypothesis that the increased risk of onset and exacerbation of OCD in women post-partum may be a result of the decrease in the level of estradiol, which was elevated during pregnancy.

Attenuation of high sweet solution preference by mood stabilizers: a possible mouse model for the increased reward-seeking domain of mania.

The lack of appropriate animal models for bipolar disorder (BPD) is a major factor hindering the research of its pathophysiology and the development of new drug treatments. In line with the notion that BPD might represent a heterogeneous group of disorders, it was suggested that models for specific domains of BPD should be developed and then integrated. The present study tested sweet solution preference as a rodent model for increased reward seeking, a central component of manic behavior and a possible endophenotype of the disorder. The study identified that Black Swiss mice show high baseline saccharin preference compared with C57bl/6, CBA/J and A/J strains. Sweet solution preference in Black Swiss mice was therefore evaluated across a number of saccharin concentrations, with or without treatment with the mood stabilizers lithium and valproate and the antidepressant imipramine. Results indicated that the structurally dissimilar mood stabilizers lithium and valproate, but not the antidepressant imipramine, reduce sweet solution preference. However, different dosing schedules were needed for the two drugs to induce this effect. These findings support the face and the predictive validity of the sweet solution preference test as an animal model for the elevated reward-seeking domain of mania. As such, this test might be well integrated into a battery of models for different domains of BPD. Such a battery can be effectively utilized to screen new treatments, to distinguish between specific effects of different drugs, and to explore the mechanisms underlying BPD.

Behavioral effects of Bcl-2 deficiency: implications for affective disorders.

New hypotheses regarding affective disorders suggest a critical role for cellular resilience and plasticity. Bcl-2 is a central protein in these processes and is elevated by mood stabilizers and antidepressants. In previous studies, mice with targeted mutations of Bcl-2 showed anxiety-related behavioral changes. The present study further explored the relationship between Bcl-2 and behavior using mice with a targeted mutation but with a different background strain than previously tested. Bcl-2 heterozygous mice (B6;129S2-Bcl-2/J) were tested in models of depression, mania and anxiety. Compared to Wild Type (WT) controls, mutant mice showed behaviors modeling two facets of mania: increased reward seeking and amphetamine sensitization. Moreover, the sensitization was attenuated by chronic pretreatment with lithium. In contrast to previous data, the mutation did not affect measures of anxiety. Although data are still minimal, it supports additional studies of the role of Bcl-2 in affective and anxiety disorders. The importance of background strain in behavioral phenotypes of mutant mice is known and the current lack of effect on anxiety measures may be related to high baseline anxiety of WTanimals. More precise studies of Bcl-2 in affective and anxiety disorders will be possible when specific pharmacological modulators of Bcl-2 become available.

Strain differences in 'compulsive' lever-pressing.

In the signal attenuation rat model of obsessive-compulsive disorder, 'compulsive' behavior is induced by attenuating a signal indicating that a lever-press response was effective in producing food. In recent years several studies have reported that Lewis rats, an inbred strain derived from the Sprague Dawley strain, exhibit addictive and/or compulsive tendencies. The aim of the present study was thus to test whether Lewis rats will also show increased compulsivity in the signal attenuation model. Because the model has been developed and validated using Wistar rats only, the present study compared the behavioral response to signal attenuation of Lewis, Sprague Dawley and Wistar rats, and assessed the effects of the anti-compulsive drug paroxetine on compulsive behavior in Lewis and Sprague Dawley rats. The results show that Lewis rats are more 'compulsive' than Sprague Dawley and Wistar rats in terms of both higher levels of compulsive lever-pressing and higher resistance to the anti-compulsive effect of paroxetine. The possibility that these strain differences are related to strain differences in the serotonergic and dopaminergic systems are discussed in light of current knowledge of the pathophysiology and pharmacotherapy of OCD.

Partial effects of the AMPAkine CX717 in a strain specific battery of tests for manic-like behavior in black Swiss mice.

BACKGROUND: AMPA receptors are highly expressed throughout the central nervous system and are suggested to be involved in mood regulation. Studies found changes in glutamate, its metabolites and receptors in patients with bipolar disorder (BPD) or major depression (MD) and in animal models of stress. Additional data suggest that the glutamatergic system and AMPA receptors specifically, have an important role in modulating the therapeutic effects of mood stabilizers. Further research on the role of AMPA receptors in mood regulation can be done using AMPAkines, positive modulators of AMPA receptors. AMPAkines have been studied for cognitive enhancement in neurodegenerative disorders and some were also examined in preclinical studies of mood disorders. In that context, the present study was designed to test the effects of the AMPAkine CX717 in a strain specific battery of tests for mania-like behaviors. METHODS: Black Swiss male mice were sub-chronically treated with 5 different doses of CX717 or vehicle and tested in a battery of behavioral tests including spontaneous activity, sweet solution preference, resident-intruder, forced swim and amphetamine-induced hyperactivity. RESULTS: Data show that CX717 doses of 30mg/kg and above, but not lower, reduce activity levels. Moreover, 45mg/kg and above reduce interactions in the resident-intruder test and ameliorate amphetamine-induced hyperactivity. CONCLUSIONS: The results therefore show a partial effect of CX717 on manic-like behavior, somewhat similar to previously demonstrated effects of atypical antipsychotic drugs in this strain. It is therefore suggested that further work related to AMPAkines in the treatment of affective disorders might be warranted.

Modeling mania: Further validation for Black Swiss mice as model animals.

The paucity of appropriate animal models for bipolar disorder hinders the research of the disorder and its treatments. Previous work suggests that Black Swiss (BS) mice may be a suitable model animal for behavioral domains of mania including reward-seeking, risk-taking, vigor, aggression and sensitivity to psychostimulants. These behaviors are high in BS mice compared with other strains and are responsive to the mood stabilizers lithium and valproate but not to the antidepressant imipramine. The current study evaluated the etiological validity of this model by assessing brain expression of two proteins implicated in affective disorders, ß-catenin and BDNF, in BS mice versus C57bl/6, A/J and CBA/J mice. Additionally, pharmacological validity was further tested by assessing the effects of risperidone in a behavioral battery of tests. ß-catenin and BDNF expression were evaluated in the frontal cortex and hippocampus of untreated BS, CBA/J, A/J and C57bl/6 mice by western blot. Subchronic 0.1 and 0.3mg/kg doses of risperidone were tested in a battery of behavioral tests for domains of mania. Expression of ß-catenin was found to be lower in the hippocampus of BS mice compared with the other strains. Reduced ß-catenin expression was not observed in the frontal cortex. BDNF expression levels were similar between strains in both the hippocampus and frontal cortex. In the behavioral tests, risperidone ameliorated amphetamine-induced hyperactivity without affecting other tests in the battery. These results offer additional pharmacological and possible etiological validity supporting the utilization of Black Swiss mice as a model for domains of mania.

Strain-specific battery of tests for domains of mania: effects of valproate, lithium and imipramine.

The lack of efficient animal models for bipolar disorder (BPD), especially for the manic pole, is a major factor hindering the research of its pathophysiology and the development of improved drug treatments. The present study was designed to identify an appropriate mouse strain for modeling some behavioral domains of mania and to evaluate the effects of drugs using this strain. The study compared the behavior of four strains: Black Swiss, C57Bl/6, CBA/J and A/J mice in a battery of tests that included spontaneous activity; sweet solution preference; light/dark box; resident-intruder; forced-swim and amphetamine-induced hyperactivity. Based on the 'manic-like' behavior demonstrated by the Black Swiss strain, the study evaluated the effects of the mood stabilizers valproate and lithium and of the antidepressant imipramine in the same tests using this strain. Results indicated that lithium and valproate attenuate the 'manic-like' behavior of Black Swiss mice whereas imipramine had no effects. These findings suggest that Black Swiss mice might be a good choice for modeling several domains of mania and distinguishing the effects of drugs on these specific domains. However, the relevance of the behavioral phenotype of Black Swiss mice to the biology of BPD is unknown at this time and future studies will investigate molecular differences between Black Swiss mice and other strains and asess the interaction between strain and mood stabilizing treatment.

Antidepressant-like effects of the active acidic polysaccharide portion of ginseng in mice.

AIM OF THE STUDY: The biological of activity of Panax ginseng C.A. Meyer (ginseng) is complex but some of its known effects are related to affective and anxiety disorders, including the enhancement of neuroprotection, cellular resilience and plasticity. Whereas such effects suggest that ginseng might have antidepressant activity, previous studies show incongruent results. The sources of contrasting results might be many but one possibility is the utilization of different ginseng preparations in different studies. The current study was therefore designed to examine the effects of a very specific component of ginseng extract, the acidic polysaccharide portion of the plant (WGPA), containing arabinogalactan, type-I rhamnogalacturonan (RG-I)- and homogalacturonan (HG)-rich pectins. MATERIALS AND METHODS: WGPA was extracted from ginseng roots and administered orally to mice at 100 mg/kg and 200 mg/kg doses. WGPA was administered chronically, once daily for 1 week before the start of experiments and throughout the behavioral tests battery. Mice were tested for spontaneous activity, social interactions, anxiety-like behavior in the elevated plus-maze (EPM) and despair-like behavior in the forced swim test (FST). RESULTS: WGPA had no effects on spontaneous activity or behavior in the EPM. In contrast, 100 mg/kg (but not the 200 mg/kg) WGPA significantly reduced immobility time in the FST and both doses significantly increased social interactions and decreased aggressive behaviors in mice. CONCLUSION: These results suggest that chronic WGPA treatment might have antidepressant-like effects that are unrelated to generalized behavioral changes. The results are discussed in the context of the known ability of the active ingredients of ginseng to increase neuroprotection, similar to many of the current antidepressant and mood stabilizing drugs.

A possible utilization of the mice forced swim test for modeling manic-like increase in vigor and goal-directed behavior.

INTRODUCTION: The lack of appropriate animal models for bipolar disorder (BPD) is a major factor hindering the research of its pathophysiology and the development of new drug treatments. In line with the notion that BPD might represent a heterogeneous group of disorders, it was suggested that models for specific domains of BPD should be developed. The present study tested the possible utilization of the forced swim test (FST) as a model for the heightened vigor and goal-directed behavior domain of mania, using mice with low baseline immobility. METHODS: Black Swiss mice were previously identified to have low immobility in the FST but similar spontaneous activity levels compared with several other mice strains. Thus, spontaneous activity and behavior in the FST were evaluated following treatment with the mood stabilizer valproate and the antidepressant imipramine. RESULTS: The results indicated that valproate increased immobility in the FST without affecting spontaneous activity whereas imipramine had no effect in the FST but increased spontaneous activity. DISCUSSION: These findings suggest that in mice with low baseline immobility scores, the FST might be a useful model for the elevated vigor and goal-directed behavior domain of mania. As such, this test might be well integrated into a battery of models for different domains of BPD.

The role of 5-HT2A and 5-HT2C receptors in the signal attenuation rat model of obsessive-compulsive disorder.

Serotonin 5-HT2A and 5-HT2C receptors have been implicated in the pathophysiology of obsessive-compulsive disorder (OCD) and in the mechanism mediating the anti-compulsive effects of serotonin reuptake inhibitors. Yet it is currently unclear whether activation or blockade of these receptors would have an anti-compulsive effect. The present study tested the effects of 5-HT2A and 5-HT2C activation and blockade in the signal attenuation rat model of OCD. In this model, 'compulsive' behaviour is induced by attenuating a signal indicating that a lever-press response was effective in producing food. Experiments1-4 revealed that systemic administration of the 5-HT2C antagonist RS 102221 (2 mg/kg) selectively decreases compulsive lever-pressing, whereas systemic administration of the 5-HT2A antagonist MDL11,939(0.2-5 mg/kg) or of the 5-HT2A/2C agonist DOI (0.05-5 mg/kg) did not have a selective effect on this behaviour. Experiments 5 and 6 found that systemic co-administration of DOI (0.5 mg/kg) withMDL11,939 (1 mg/kg) or with RS 102221 (2 mg/kg) had a non-selective effect on lever-press responding,with the former manipulation increasing and the latter manipulation decreasing lever-pressing. Finally,experiment 7 demonstrated that administration of RS 102221 directly into the orbitofrontal cortex also exerts an anti-compulsive effect. The results of these experiments suggest that blockade of 5-HT2Creceptors may have an anti-compulsive effect in OCD patients, and that this effect may be mediated by5-HT2C receptors within the orbitofrontal cortex.