Showing papers in "Psychopharmacology in 2011"

Effects of early life stress on cognitive and affective function: an integrated review of human literature.

Abstract: Rationale The investigation of putative effects of early life stress (ELS) in humans on later behavior and neurobiology is a fast developing field. While epidemiological and neurobiological studies paint a somber picture of negative outcomes, relatively little attention has been devoted to integrating the breadth of findings concerning possible cognitive and emotional deficits associated with ELS. Emerging findings from longitudinal studies examining developmental trajectories of the brain in healthy samples may provide a new framework to understand mechanisms underlying ELS sequelae.

Delayed reward discounting and addictive behavior: a meta-analysis

Abstract: Rationale Delayed reward discounting (DRD) is a behavioral economic index of impulsivity and numerous studies have examined DRD in relation to addictive behavior. To synthesize the findings across the literature, the current review is a meta-analysis of studies comparing DRD between criterion groups exhibiting addictive behavior and control groups.

Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects

Abstract: Rationale This dose-effect study extends previous observations showing that psilocybin can occasion mystical-type experiences having persisting positive effects on attitudes, mood, and behavior.

The role of early life stress as a predictor for alcohol and drug dependence

Abstract: Rationale Genetic and environmental influences on the development of alcohol and drug dependence are equally important. Exposure to early life stress, that is unfortunately common in the general population, has been shown to predict a wide range of psychopathology, including addiction.

Stressful life experiences, alcohol consumption, and alcohol use disorders: the epidemiologic evidence for four main types of stressors

Abstract: Background Exposure to stress is potentially important in the pathway to alcohol use and alcohol use disorders. Stressors occur at multiple time points across the life course, with varying degrees of chronicity and severity.

Maternal separation as a model of brain–gut axis dysfunction

Abstract: Early life stress has been implicated in many psychiatric disorders ranging from depression to anxiety. Maternal separation in rodents is a well-studied model of early life stress. However, stress during this critical period also induces alterations in many systems throughout the body. Thus, a variety of other disorders that are associated with adverse early life events are often comorbid with psychiatric illnesses, suggesting a common underlying aetiology. Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that is thought to involve a dysfunctional interaction between the brain and the gut. Essential aspects of the brain–gut axis include spinal pathways, the hypothalamic pituitary adrenal axis, the immune system, as well as the enteric microbiota. Accumulating evidence suggest that stress, especially in early life, is a predisposing factor to IBS. The objective of this review was to assess and compile the most relevant data on early life stress and alterations at all levels of the brain gut axis. In this review, we describe the components of the brain–gut axis individually and how they are altered by maternal separation. The separated phenotype is characterised by alterations of the intestinal barrier function, altered balance in enteric microflora, exaggerated stress response and visceral hypersensitivity, which are all evident in IBS. Thus, maternally separated animals are an excellent model of brain–gut axis dysfunction for the study of disorders such as IBS and for the development of novel therapeutic interventions.

Mephedrone (4-methylmethcathinone; 'meow meow'): chemical, pharmacological and clinical issues.

Abstract: Background Recently, those substances deriving from the active ingredient of the Khat plant, cathinone, have been rising in popularity. Indeed, 4-methylmethcathinone (mephedrone; ‘meowmeow’and others) has beenseenbysomeasa cheaper alternative to other classified recreational drugs. Aims We aimed here at providing a state-of-the-art review on mephedrone history and prevalence of misuse, chemistry,

Effect of childhood physical abuse on cortisol stress response

Abstract: Rationale Abuse and neglect are highly prevalent in children and have enduring neurobiological effects. Stressful early life environments perturb the hypothalamic–pituitary–adrenal (HPA) axis, which in turn may predispose to psychiatric disorders in adulthood. However, studies of childhood maltreatment and adult HPA function have not yet rigorously investigated the differential effects of maltreatment subtypes, including physical abuse.

Gene–environment interactions: early life stress and risk for depressive and anxiety disorders

Abstract: Rationale Prior reviews have examined how stress, broadly defined, interacts with genetic diathesis in the pathogenesis of internalizing (i.e., depressive and anxiety) disorders. Recent findings have suggested a unique role for early life stress (ELS) in the development of internalizing disorders, contributing to the rapid proliferation of research in this area.

Prenatal stress: role in psychotic and depressive diseases.

Abstract: Rationale The birth of neurons, their migration to appropriate positions in the brain, and their establishment of the proper synaptic contacts happen predominately during the prenatal period. Environmental stressors during gestation can exert a major impact on brain development and thereby contribute to the pathogenesis of neuropsychiatric illnesses, such as depression and psychotic disorders including schizophrenia.

Functional topography of midbrain and pontine serotonergic systems: implications for synaptic regulation of serotonergic circuits

Abstract: Dysfunction of serotonergic systems is thought to play an important role in a number of neurological and psychiatric disorders. Recent studies suggest that there is anatomical and functional diversity among serotonergic systems innervating forebrain systems involved in the control of physiologic and behavioral responses, including the control of emotional states. Here, we highlight the methods that have been used to investigate the heterogeneity of serotonergic systems and review the evidence for the unique anatomical, hodological, and functional properties of topographically organized subpopulations of serotonergic neurons in the midbrain and pontine raphe complex. The emerging understanding of the topographically organized synaptic regulation of brainstem serotonergic systems, the topography of the efferent projections of these systems, and their functional properties, should enable identification of novel therapeutic approaches to treatment of neurological and psychiatric conditions that are associated with dysregulation of serotonergic systems.

The role of serotonin receptor subtypes in treating depression: a review of animal studies.

Abstract: Rationale Serotonin reuptake inhibitors (SSRIs) are effective in treating depression. Given the existence of different families and subtypes of 5-HT receptors, multiple 5-HT receptors may be involved in the antidepressant-like behavioral effects of SSRIs.

Effects of stress on alcohol drinking: a review of animal studies

Abstract: Rationale While stress is often proposed to play a significant role in influencing alcohol consumption, the relationship between stress and alcohol is complex and poorly understood. Over several decades, stress effects on alcohol drinking have been studied using a variety of animal models and experimental procedures, yet this large body of literature has generally produced equivocal results.

Verbal learning and memory in adolescent cannabis users, alcohol users and non-users

Abstract: Rationale Long-term heavy cannabis use can result in memory impairment. Adolescent users may be especially vulnerable to the adverse neurocognitive effects of cannabis. Objectives and methods In a cross-sectional and prospective neuropsychological study of 181 adolescents aged 16–20 (mean 18.3 years), we compared performance indices from one of the most widely used measures of learning and memory—the Rey Auditory Verbal Learning Test—between cannabis users (n=52; mean 2.4 years of use, 14 days/month, median abstinence 20.3 h), alcohol users (n=67) and non-user controls (n=62) matched for age, education and premorbid intellectual ability (assessed prospectively), and alcohol consumption for cannabis and alcohol users. Results Cannabis users performed significantly worse than alcohol users and non-users on all performance indices. They recalled significantly fewer words overall (p<0.001), demonstrating impaired learning (p<0.001), retention (p<0.001) and retrieval (p<0.05) (Cohen’s d 0.43–0.84). The degree of impairment was associated with the duration, quantity, frequency and age of onset of cannabis use, but was unrelated to alcohol exposure or other drug use. No gender effects were detected and the findings remained after controlling for premorbid intellectual ability. An earlier age of onset of regular cannabis use was associated with worse memory performance after controlling for extent of exposure to cannabis. Conclusions Despite relatively brief exposure, adolescent cannabis users relative to their age-matched counterparts demonstrated similar memory deficits to those reported in adult long-term heavy users. The results indicate that cannabis adversely affects the developing brain and reinforce concerns regarding the impact of early exposure.

Translational and reverse translational research on the role of stress in drug craving and relapse.

Abstract: Rationale and background High relapse rates during abstinence are a pervasive problem in drug addiction treatment. Relapse is often associated with stress exposure, which can provoke a subjective state of drug craving that can also be demonstrated under controlled laboratory conditions. Stress-induced relapse and craving in humans can be modeled in mice, rats, and monkeys using a reinstatement model in which drug-taking behaviors are extinguished and then reinstated by acute exposure to certain stressors. Studies using the reinstatement model in rats have identified the role of several neurotransmitters and brain sites in stress-induced reinstatement of drug seeking, but the degree to which these preclinical findings are relevant to the human condition is largely unknown.

Fluoxetine regulates the expression of neurotrophic/growth factors and glucose metabolism in astrocytes

Abstract: Rationale The pharmacological actions of most antidepressants are ascribed to the modulation of serotonergic and/or noradrenergic transmission in the brain. During therapeutic treatment for major depression, fluoxetine, one of the most commonly prescribed selective serotonin reuptake inhibitor (SSRI) antidepressants, accumulates in the brain, suggesting that fluoxetine may interact with additional targets. In this context, there is increasing evidence that astrocytes are involved in the pathophysiology of major depression.

Cannabidiol potentiates Δ9-tetrahydrocannabinol (THC) behavioural effects and alters THC pharmacokinetics during acute and chronic treatment in adolescent rats

Abstract: Rationale The interactions between Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) during chronic treatment, and at equivalent doses, are not well characterised in animal models.

Hypocretin 1/orexin A in the ventral tegmental area enhances dopamine responses to cocaine and promotes cocaine self-administration

Abstract: Rationale Recent evidence indicates that the hypocretin/orexin system participates in the regulation of reinforcement and addiction processes. For example, manipulations that decrease hypocretin neurotransmission result in disruptions of neurochemical and behavioral responses to cocaine.

Stress in the daily lives of cocaine and heroin users: relationship to mood, craving, relapse triggers, and cocaine use

Abstract: Rationale Quantitative real-time data on the stress experienced by drug misusers in their daily lives may provide additional insight into stress’s role in drug use

Early life stress paradigms in rodents: potential animal models of depression?

Abstract: Rationale While human depressive illness is indeed uniquely human, many of its symptoms may be modeled in rodents Based on human etiology, the assumption has been made that depression-like behaviorinratsand micecan bemodulated by some of the powerful early life programming effects that are known to occur after manipulations in the first weeks of life Objective Here we review the evidence that is available in literature for early life manipulation as risk factors for the development of depression-like symptoms such as anhedonia, passive coping strategies, and neuroendocrine changes Early life paradigms that were evaluated include early handling, separation, and deprivation protocols, as well as enriched and impoverished environments We have also included a small number of stress-related pharmacological models Results We find that for most early life paradigms per se, the actual validity for depression is limited A number of models have not been tested with respect to classical depression-like behaviors, while in many cases, the outcome of such experiments is variable and depends on strain and additional factors Conclusion Because programming effects confer vulnerability rather than disease, a number of paradigms hold promise for usefulness in depression research, in combination with the proper genetic background and adult life challenges

Neuropsychopharmacological effect of sesamol in unpredictable chronic mild stress model of depression: behavioral and biochemical evidences

Abstract: Rationale A complex relationship exists among stressful situations, body's reaction to stress, and the onset of clinical depression. Chronic unpredictable stressors can produce a situation similar to clinical depression, and such animal models can be used for the preclinical evaluation of antidepressants. Many findings have shown that the levels of proinflammatory cytokines (e.g., TNF-α) and oxidative stress (increased lipid peroxidation, decreased glutathione levels, and endogenous antioxidant enzyme activities) are increased in patients with depression. Sesamol, a phenolic derivative with a methylenedioxy group, is a potent inhibitor of cytokine production as well as an antioxidant.

The anxiolytic-like effects of cannabidiol injected into the bed nucleus of the stria terminalis are mediated by 5-HT1A receptors

Abstract: Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa that induces anxiolytic-like effects in rodents and humans after systemic administration. Previous results from our group showed that CBD injection into the bed nucleus of the stria terminalis (BNST) attenuates conditioned aversive responses. The aim of this study was to further investigate the role of this region on the anxiolytic effects of the CBD. Moreover, considering that CBD can activate 5-HT1A receptors, we also verified a possible involvement of these receptors in those effects. Male Wistar rats received injections of CBD (15, 30, or 60 nmol) into the BNST and were exposed to the elevated plus-maze (EPM) or to the Vogel conflict test (VCT), two widely used animal models of anxiety. CBD increased open arms exploration in the EPM as well as the number of punished licks in the VCT, suggesting an anxiolytic-like effect. The drug did not change the number of entries into the enclosed arms of the EPM nor interfered with water consumption or nociceptive threshold, discarding potential confounding factors in the two tests. Moreover, pretreatment with the 5-HT1A receptor antagonist WAY100635 (0.37 nmol) blocked the effects of CBD in both models. These results give further support to the proposal that BNST is involved in the anxiolytic-like effects of CBD observed after systemic administration, probably by facilitating local 5-HT1A receptor-mediated neurotransmission.

Selective blockade of the orexin-2 receptor attenuates ethanol self-administration, place preference, and reinstatement.

Abstract: Rationale Orexin-1 receptor antagonists have been shown to block the reinforcing effects of drugs of abuse and food. However, whether blockade of orexin-2 receptor has similar effects has not been determined. We have recently described the in vitro and in vivo effects of JNJ-10397049, a selective and brain penetrant orexin-2 receptor antagonist.

Comparative pharmacology of antipsychotics possessing combined dopamine D2 and serotonin 5-HT1A receptor properties.

Abstract: Rationale There is increasing interest in antipsychotics intended to manage positive symptoms via D2 receptor blockade and improve negative symptoms and cognitive deficits via 5-HT1A activation. Such a strategy reduces side-effects such as the extrapyramidal syndrome (EPS), weight gain, and autonomic disturbance liability.

Chronic agomelatine treatment corrects behavioral, cellular, and biochemical abnormalities induced by prenatal stress in rats.

Abstract: Rationale and objectives The rat model of prenatal restraint stress (PRS) replicates factors that are implicated in the etiology of anxious/depressive disorders. We used this model to test the therapeutic efficacy of agomelatine, a novel antidepressant that behaves as a mixed MT1/MT2 melatonin receptor agonist/5-HT2c serotonin receptor antagonist.

Cigarette demand and delayed reward discounting in nicotine-dependent individuals with schizophrenia and controls: an initial study

Abstract: Rationale The high prevalence of smoking and low cessation rates among individuals with schizophrenia and similar conditions are not well understood. Behavioral economics has been extensively applied to studying addictive behavior and may contribute to understanding smoking in this subpopulation.

Fluoxetine administration to pregnant rats increases anxiety-related behavior in the offspring

Abstract: Rationale Fluoxetine (Prozac®) is the most frequently prescribed drug to battle depression in pregnant women, but its safety in the unborn child has not yet been established. Fluoxetine, a selective serotonin reuptake inhibitor, crosses the placenta, leading to increased extracellular serotonin levels and potentially neurodevelopmental changes in the fetus.

Early maternal deprivation affects dentate gyrus structure and emotional learning in adult female rats.

Abstract: Rationale Stress elicits functional and structural changes in the hippocampus. Early life stress is one of the major risk factors for stress-related pathologies like depression. Patients suffering from depression show a reduced hippocampal volume, and in women, this occurs more often when depression is preceded by childhood trauma. However, the underlying mechanisms that account for a reduced hippocampal volume are unknown.

Tolerance and cross-tolerance to neurocognitive effects of THC and alcohol in heavy cannabis users

Abstract: Introduction Previous research has shown that heavy cannabis users develop tolerance to the impairing effects of Δ9-tetrahydrocannabinol (THC) on neurocognitive functions. Animal studies suggest that chronic cannabis consumption may also produce cross-tolerance for the impairing effects of alcohol, but supportive data in humans is scarce. Purpose The present study was designed to assess tolerance and cross-tolerance to the neurocognitive effects of THC and alcohol in heavy cannabis users. Methods Twenty-one heavy cannabis users participated in a double-blind, placebo-controlled, three-way study. Subjects underwent three alcohol-dosing conditions that were designed to achieve a steady blood alcohol concentration of about 0, 0.5, and 0.7 mg/ml during a 5-h time window. In addition, subjects smoked a THC cigarette (400 μg/kg) at 3 h post-onset of alcohol dosing during every alcohol condition. Performance tests were conducted repeatedly between 0 and 7 h after onset of drinking and included measures of perceptual motor control (critical tracking task), dual task processing (divided-attention task), motor inhibition (stop-signal task), and cognition (Tower of London). Results Alcohol significantly impaired critical tracking, divided attention, and stop-signal performance. THC generally did not affect task performance. However, combined effects of THC and alcohol on divided attention were bigger than those by alcohol alone. Conclusion In conclusion, the present study generally confirms that heavy cannabis users develop tolerance to the impairing effects of THC on neurocognitive task performance. Yet, heavy cannabis users did not develop cross-tolerance to the impairing effects of alcohol, and the presence of the latter even selectively potentiated THC effects on measures of divided attention.

A preliminary investigation of varenicline for heavy drinking smokers.

Abstract: Rationale Varenicline, an approved smoking cessation pharmacotherapy, also shows promise as a potential treatment for alcohol dependence. However, varenicline has not been tested in heavy drinkers, and it remains to be determined whether varenicline could reduce alcohol craving and consumption in smokers who are trying to quit smoking.