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Anxiolytic Effects (anxiolytic + effects)
Selected AbstractsAnxiolytic effects of a combination of Melissa ofcinalis and Valeriana ofcinalis during laboratory induced stressPHYTOTHERAPY RESEARCH, Issue 2 2006David O. Kennedy Abstract Objective: Melissa ofcinalis (lemon balm) and Valeriana ofcinalis (valerian) have been used both traditionally and contemporaneously as mild sedatives, anxiolytics and hypnotics. Recent research has suggested that both may attenuate laboratory induced stress. As the two herbs are most often sold in combination with each other the current study assessed the anxiolytic properties of such a combination during laboratory-induced stress. Methods: In this double-blind, placebo-controlled, randomized, balanced cross-over experiment, 24 healthy volunteers received three separate single doses (600 mg, 1200 mg, 1800 mg) of a standardized product containing M. ofcinalis and V. ofcinalis extracts, plus a placebo, on separate days separated by a 7 day wash out period. Modulation of mood and anxiety were assessed during pre-dose and 1 h, 3 h and 6 h post-dose completions of a 20 min version of the Dened Intensity Stressor Simulation (DISS) battery. Cognitive performance on the four concurrent tasks of the battery was also assessed. Results: The results showed that the 600 mg dose of the combination ameliorated the negative effects of the DISS on ratings of anxiety. However, the highest dose (1800 mg) showed an increase in anxiety that was less marked but which reached signicance during one testing session. In addition, all three doses led to decrements in performance on the Stroop task module within the battery, and the two lower doses led to decrements on the overall score generated on the DISS battery. Conclusions: These results suggest that a combination of Melissa ofcinalis and Valeriana ofcinalis possesses anxiolytic properties that deserve further investigation. Copyright © 2006 John Wiley & Sons, Ltd. [source] REVIEW: Alcohol-related genes: contributions from studies with genetically engineered miceADDICTION BIOLOGY, Issue 3-4 2006John C. Crabbe ABSTRACT Since 1996, nearly 100 genes have been studied for their effects related to ethanol in mice using genetic modifications including gene deletion, gene overexpression, gene knock-in, and occasionally by studying existing mutants. Nearly all such studies have concentrated on genes expressed in brain, and the targeted genes range widely in their function, including most of the principal neurotransmitter systems, several neurohormones, and a number of signaling molecules. We review 141 published reports of effects (or lack thereof) of 93 genes on responses to ethanol. While most studies have focused on ethanol self-administration and reward, and/or sedative effects, other responses studied include locomotor stimulation, anxiolytic effects, and neuroadaptation (tolerance, sensitization, withdrawal). About 1/4 of the engineered mutations increase self-administration, 1/3 decrease it, and about 40% have no significant effect. In many cases, the effects on self-administration are rather modest and/or depend on the specific experimental procedures. In some cases, genes in the background strains on which the mutant is placed are important for results. Not surprisingly, review of the systems affected further supports roles for serotonin, ,-aminobutyric acid, opioids and dopamine, all of which have long been foci of alcohol research. Novel modulatory effects of protein kinase C and G protein-activated inwardly rectifying K+ (GIRK) channels are also suggested. Some newer research with cannabinoid systems is promising, and has led to ongoing clinical trials. [source] Does rat global transient cerebral ischemia serve as an appropriate model to study emotional disturbances?FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 6 2004Guy Bernard Bantsiele Abstract We used two validated psychopharmacological methods, the forced swimming test (FST 20 min and 5 min) and the elevated plus-maze (EPM), to quantify depression-like and anxiety-like behavior induced by transient global cerebral ischemia in the rat. We also validated use of these methods for the study of antidepressant (imipramine) and anti-anxiety drugs (diazepam). Twelve days after surgery to provoke transient global ischemia, spontaneous motor activity was 40% higher in ischemic rats than in sham-operated controls. Duration of immobility during the FST 20 min and 5 min was 28 and 30% shorter, respectively, than in controls. Treatment with imipramine (3 × 30 mg/kg i.p.) induced a significantly shorter duration of immobility during the FST 5 min, but with no difference between ischemia and control rats. The EPM demonstrated that ischemia did not induce any change in the six behavior parameters measured. Diazepam (1.5 mg/kg i.p.) induced significant anxiolytic effects which were similar in ischemic and sham-operated animals. Both tests failed to demonstrate perturbed performance but conversely, these findings did disclose the sensitivity of ischemia-exposed rats to the action of imipramine and diazepam, demonstrating the usefulness of these tests as psychopharmocological tools for evaluating the effect of psychotropics in the ischemic rat. [source] Neuropeptide Y Signaling in the Central Nucleus of Amygdala Regulates Alcohol-Drinking and Anxiety-Like Behaviors of Alcohol-Preferring RatsALCOHOLISM, Issue 3 2010Huaibo Zhang Background:, The neuropeptide Y (NPY) system of the central nucleus of amygdala (CeA) has been shown to be involved in anxiety and alcoholism. In this study, we investigated the molecular mechanisms by which NPY in the CeA regulates anxiety and alcohol drinking behaviors using alcohol-preferring (P) rats as an animal model. Methods:, Alcohol-preferring rats were bilaterally cannulated targeting the CeA and infused with artificial cerebrospinal fluid (aCSF) or NPY. Alcohol drinking and anxiety-like behaviors were assessed by the 2-bottle free-choice paradigm and light/dark box (LDB) exploration test, respectively. The levels of NPY and related signaling proteins were determined by the gold immunolabeling procedure. The mRNA levels of NPY were measured by in situ RT-PCR. Double-immunofluorescence labeling was performed to observe the colocalization of NPY and Ca2+/calmodulin-dependent protein kinase IV (CaMK IV). Results:, We found that NPY infusion into the CeA produced anxiolytic effects, as measured by the LDB exploration test, and also decreased alcohol intake in P rats. NPY infusion into the CeA significantly increased levels of CaMK IV and phosphorylated cAMP responsive element-binding (pCREB) protein and increased mRNA and protein levels of NPY, but produced no changes in protein levels of CREB or the catalytic ,-subunit of protein kinase A (PKA-C,) in the CeA. We also observed that alcohol intake produced anxiolytic effects in P rats in the LDB test and also increased NPY expression and protein levels of pCREB and PKA-C, without modulating protein levels of CREB or CaMK IV, in both the CeA and medial nucleus of amygdala. In addition, we found that CaMK IV-positive cells were co-localized with NPY in amygdaloid structures of P rats. Conclusions:, These results suggest that NPY infusion may increase the expression of endogenous NPY in the CeA, which is most likely attributable to an increase in CaMK IV-dependent CREB phosphorylation and this molecular mechanism may be involved in regulating anxiety and alcohol drinking behaviors of P rats. [source] Neuropeptide S Receptor Gene Expression in Alcohol Withdrawal and Protracted Abstinence in Postdependent RatsALCOHOLISM, Issue 1 2010Barbara Ruggeri Background:, Alcoholism is a chronic disease characterized by frequent intoxications followed by withdrawal episodes and relapse to alcohol use. Neuroplastic changes associated with these intoxication and withdrawal cycles are thought to play a key role in disease progression. Recently, it has been shown that neuropeptide S (NPS), a newly deorphanized neuropeptide receptor system, facilitates relapse to alcohol seeking in laboratory animals. Given that a history of ethanol intoxication may increase vulnerability to alcohol addiction, we sought to determine whether NPS receptor (NPSR) gene expression is altered during withdrawal. Methods:, Rats were subjected to 1 week of intoxication by oral alcohol administration. NPSR gene expression was analyzed by in situ hybridization in rats 12 hours and 7 days after the last alcohol administration. To investigate the functional significance of NPSR system adaptation following protracted withdrawal 7 days after intoxication, we tested the anxiolytic-like properties of NPS in nondependent and postdependent rats using the shock probe defensive burying test (DB). Results:, At both time points, increased NPSR gene expression was observed in several brain areas, including the endopiriform nucleus, the motor cortex, and the medial amygdaloid nucleus. Moderate increases in gene expression were also found in the lateral hypothalamus, paraventricular nucleus, basolateral and central amygdala. Differences from control animals were more pronounced after 7 days of abstinence. The upregulation of the NPSR system at this time point was confirmed by functional data indicating that intracerebroventricular (ICV) NPS administration (0.0, 0.3, and 0.1 nmol/rat) elicits more pronounced anxiolytic effects in postdependent animals than in controls subjected to the electric shock probe DB test. Conclusions:, Neuropeptide S receptor mRNA expression is increased in different brain areas of postdependent rats; as shown in the DB test, this expression change is functionally relevant. [source] Immediate Benefits of a Brief 10-Minute Exercise Protocol in a Chronic Pain Population: A Pilot StudyPAIN MEDICINE, Issue 4 2010Amy Burleson Sullivan PsyD Abstract Objective., Determining the acute effects of a brief, 10-minute exercise protocol on pain, mood, and perceived exertion. Patients., Twenty-eight subjects who were admitted to the Cleveland Clinic Chronic Pain Rehabilitation Program (CPRP), and who were capable of completing an experimenter-designed and controlled treadmill protocol were included in this pilot study. Methods., A within-group repeated measure analysis was used to compare 28 subjects admitted to the Cleveland Clinic CPRP. Measures of heart rate were obtained using the Nellcor Oximax, pulse oximeter; measures of mood and pain were obtained using a 0,10 Likert scale, and perceived exertion measured with a visual analog scale. Each measure was taken pre- and post-10-minute exercise protocol. Results., The brief exercise protocol was associated with self-report of immediate antidepressant and anxiolytic effects. Additionally, after the 3-week CPRP, self-reports in perceived exertion decreased. Brief exercise was not found to have an acute analgesic effect. Conclusion., This preliminary research revealed a temporal association of improvement in self-rated anxiety and depression, following a brief exercise protocol, and over the course of 3 weeks leads to decreased perceived exertion. Therefore suggesting that brief exercise is a safe, nonpharmacologic strategy for immediately improving mood, and has further implications for mortality risk. [source] Recent advances in the neurobiology of anxiety disorders: Implications for novel therapeutics,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 2 2008Sanjay J. Mathew Abstract Anxiety disorders are a highly prevalent and disabling class of psychiatric disorders. This review focuses on new directions in neurobiological research and implications for the development of novel psychopharmacological treatments. Neuroanatomical and neuroimaging research in anxiety disorders has centered on the role of the amygdala, reciprocal connections between the amygdala and the prefrontal cortex, and, most recently, alterations in interoceptive processing by the anterior insula. Anxiety disorders are characterized by alterations in a diverse range of neurochemical systems, suggesting ample novel targets for drug therapies. Corticotropin-releasing factor (CRF) concentrations are elevated in a subset of anxiety disorders, which suggests the potential utility of CRF receptor antagonists. Pharmacological blockade of the memory-enhancing effects of stress hormones such as glucocorticoids and noradrenaline holds promise as a preventative approach for trauma-related anxiety. The glutamatergic system has been largely overlooked as a potential pharmacological target, although convergent preclinical, neuroimaging, and early clinical findings suggest that glutamate receptor antagonists may have potent anxiolytic effects. Glutamatergic receptor agonists (e.g., D -cycloserine) also have an emerging role in the treatment of anxiety as facilitators of fear extinction during concurrent behavioral interventions. The neuropeptides substance P, neuropeptide Y, oxytocin, orexin, and galanin are each implicated in anxiety pathways, and neuropeptide analogs or antagonists show early promise as anxiolytics in preclinical and/or clinical research. Each of these active areas of research holds promise for expanding and improving evidence-based treatment options for individuals suffering with clinical anxiety. © 2008 Wiley-Liss, Inc. [source] Anxiety, cortisol, and attachment predict plasma oxytocinPSYCHOPHYSIOLOGY, Issue 3 2007Mattie Tops Abstract Oxytocin and attachment seem to interact in suppressing subjective anxiety and physiological stress responses. In this study we investigated the relationships between individual differences in trait attachment scores, state and trait anxiety, plasma cortisol, and plasma oxytocin levels in healthy premenopausal women. Attachment proved to be a strong positive predictor of oxytocin levels, which were also positively predicted by cortisol levels and state and trait anxiety. The relationship between oxytocin and state anxiety was modulated by attachment scores. The present results may help interpreting seeming contradictions in the recent literature on oxytocin, attachment, and stress in humans, by suggesting that context effects determine which relationships are found in different studies: anxiolytic effects of oxytocin in a context of partner support versus stress- or cortisol-induced oxytocin responses in a context of distress or increased cortisol. [source] TC-5214 (S-(+)-Mecamylamine): A Neuronal Nicotinic Receptor Modulator with Antidepressant ActivityCNS: NEUROSCIENCE AND THERAPEUTICS, Issue 4 2008Patrick M. Lippiello Both clinical and preclinical data support a potential therapeutic benefit of modulating the activity of CNS neuronal nicotinic receptors (NNRs) to treat depression and anxiety disorders. Based on the notion that the depressive states involve hypercholinergic tone, we have examined the potential palliative role of NNR antagonism in these disorders, using TC-5214 (S-(+) enantiomer of mecamylamine), a noncompetitive NNR antagonist. TC-5214 demonstrated positive effects in a number of animal models of depression and anxiety. TC-5214 was active in the forced swim test in rats (minimum effective dose (MED) = 3 mg/kg i.p.), a classical depression model. It was also active in the behavioral despair test in mice (0.1,3.0 mg/kg i.p.), another model of depression. In the social interaction paradigm in rats, a model of generalized anxiety disorder (GAD), TC-5214 was active at a dose of 0.05 mg/kg s.c. In the light/dark chamber paradigm in rats, a model of GAD and phobia, TC-5214 was also active at a dose of 0.05 mg/kg s.c. Although TC-5214 shows modest selectivity among NNR subtypes, the antidepressant and anxiolytic effects seen in these studies are likely attributable to antagonist effects at the ,4,2 NNRs. This is supported by the observation of similar effects with ,4,2-selective partial agonists such as cytisine and with ,4,2-selective antagonists such as TC-2216. TC-5214 was well tolerated in acute and chronic toxicity studies in mice, rats, and dogs, showed no mutagenicity and displayed safety pharmacology, pharmacokinetic and metabolic profiles appropriate for therapeutic development. Overall, the results support a novel nicotinic cholinergic antagonist mechanism for antidepressant and anxiolytic effects and highlight the potential of NNR antagonists such as TC-5214 as therapeutics for the treatment of anxiety and depression. [source] | |||||||||||||