Neuropsychopharmacology

http://www.nature.com/npp

List of Papers (Total 323)

The olfactory bulb is a source of high-frequency oscillations (130–180 Hz) associated with a subanesthetic dose of ketamine in rodents

High-frequency neuronal population oscillations (HFO, 130–180 Hz) are robustly potentiated by subanesthetic doses of ketamine. This frequency band has been recorded in functionally and neuroanatomically diverse cortical and subcortical regions, notably ventral striatal areas. However, the locus of generation remains largely unknown. There is compelling evidence that olfactory...

NPTX2 is a key component in the regulation of anxiety

Anxiety disorders significantly impair quality of life. However, limited knowledge of the underlying mechanisms impedes the development of effective therapeutics. Previous studies have suggested that the expression of the Nptx2 gene is associated with anxiety, but the neurobiological processes underlying this association remain unclear. We generated multiple mouse models with...

Cortical inhibitory markers of lifetime suicidal behavior in depressed adolescents

Although suicide is the second-leading cause of death in adolescents and young adults worldwide, little progress has been made in developing reliable biological markers of suicide risk and suicidal behavior. Converging evidence suggests that excitatory and inhibitory cortical processes mediated by the neurotransmitters glutamate and γ-aminobutyric acid (GABA) are dysregulated in...

Multimodal Investigation of Network Level Effects Using Intrinsic Functional Connectivity, Anatomical Covariance, and Structure-to-Function Correlations in Unmedicated Major Depressive Disorder

Converging evidence suggests that major depressive disorder (MDD) affects multiple large-scale brain networks. Analyses of the correlation or covariance of regional brain structure and function applied to structural and functional MRI data may provide insights into systems-level organization and structure-to-function correlations in the brain in MDD. This study applied tensor...

A Primer on Foraging and the Explore/Exploit Trade-Off for Psychiatry Research

Foraging is a fundamental behavior, and many types of animals appear to have solved foraging problems using a shared set of mechanisms. Perhaps the most common foraging problem is the choice between exploiting a familiar option for a known reward and exploring unfamiliar options for unknown rewards—the so-called explore/exploit trade-off. This trade-off has been studied...

Effects of a Serotonin 2C Agonist and a 2A Antagonist on Actigraphy-Based Sleep Parameters Disrupted by Methamphetamine Self-Administration in Rhesus Monkeys

Sleep disorders and substance abuse are highly comorbid and we have previously shown that methamphetamine self-administration significantly disrupts activity-based sleep parameters in rhesus monkeys. To the best of our knowledge, no study has evaluated the effectiveness of any pharmacological intervention to attenuate the effects of methamphetamine on nighttime activity under...

High-Frequency Stimulation of the Subthalamic Nucleus Blocks Compulsive-Like Re-Escalation of Heroin Taking in Rats

Opioid addiction, including addiction to heroin, has markedly increased in the past decade. The cost and pervasiveness of heroin addiction, including resistance to recovery from addiction, provide a compelling basis for developing novel therapeutic strategies. Deep brain stimulation may represent a viable alternative strategy for the treatment of intractable heroin addiction...

Stress Induces a Shift Towards Striatum-Dependent Stimulus-Response Learning via the Mineralocorticoid Receptor

Stress is assumed to cause a shift from flexible 'cognitive' memory to more rigid 'habit' memory. In the spatial memory domain, stress impairs place learning depending on the hippocampus whereas stimulus-response learning based on the striatum appears to be improved. While the neural basis of this shift is still unclear, previous evidence in rodents points towards cortisol...

Ethanol-Sensitive Pacemaker Neurons in the Mouse External Globus Pallidus

Although ethanol is one of the most widely used drugs, we still lack a full understanding of which neuronal subtypes are affected by this drug. Pacemaker neurons exert powerful control over brain circuit function, but little is known about ethanol effects on these types of neurons. Neurons in the external globus pallidus (GPe) generate pacemaker activity that controls basal...

Microglia Priming with Aging and Stress

The population of aged individuals is increasing worldwide and this has significant health and socio-economic implications. Clinical and experimental studies on aging have discovered myriad changes in the brain, including reduced neurogenesis, increased synaptic aberrations, higher metabolic stress, and augmented inflammation. In rodent models of aging, these alterations are...

Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond

The study of inflammation in fear- and anxiety-based disorders has gained interest as growing literature indicates that pro-inflammatory markers can directly modulate affective behavior. Indeed, heightened concentrations of inflammatory signals, including cytokines and C-reactive protein, have been described in posttraumatic stress disorder (PTSD), generalized anxiety disorder...

Sleep Health: Reciprocal Regulation of Sleep and Innate Immunity

Sleep disturbances including insomnia independently contribute to risk of inflammatory disorders and major depressive disorder. This review and overview provides an integrated understanding of the reciprocal relationships between sleep and the innate immune system and considers the role of sleep in the nocturnal regulation of the inflammatory biology dynamics; the impact of...

Role of Adiposity-Driven Inflammation in Depressive Morbidity

Depression and metabolic disorders, including overweight and obesity, appear tightly interrelated. The prevalence of these conditions is concurrently growing worldwide, and both depression and overweight/obesity represent substantial risk factors for multiple medical complications. Moreover, there is now multiple evidence for a bidirectional relationship between depression and...

Microbes, Immunity, and Behavior: Psychoneuroimmunology Meets the Microbiome

There is now a large volume of evidence to support the view that the immune system is a key communication pathway between the gut and brain, which plays an important role in stress-related psychopathologies and thus provides a potentially fruitful target for psychotropic intervention. The gut microbiota is a complex ecosystem with a diverse range of organisms and a sophisticated...

Amygdala-Dependent Molecular Mechanisms of the Tac2 Pathway in Fear Learning

Recently we determined that activation of the tachykinin 2 (Tac2) pathway in the central amygdala (CeA) is necessary and sufficient for the modulation of fear memories. The Tac2 pathway includes the Tac2 gene, which encodes the neuropeptide neurokinin B and its corresponding receptor neurokinin 3 receptor (NK3R). In this study, using Tac2–cre and Tac2–GFP mice, we applied a...

Smoking Abstinence-Induced Changes in Resting State Functional Connectivity with Ventral Striatum Predict Lapse During a Quit Attempt

The ventral and dorsal striatum are critical substrates of reward processing and motivation and have been repeatedly linked to addictive disorders, including nicotine dependence. However, little is known about how functional connectivity between these and other brain regions is modulated by smoking withdrawal and may contribute to relapse vulnerability. In the present study, 37...

Diversity of Dopaminergic Neural Circuits in Response to Drug Exposure

Addictive substances are known to increase dopaminergic signaling in the mesocorticolimbic system. The origin of this dopamine (DA) signaling originates in the ventral tegmental area (VTA), which sends afferents to various targets, including the nucleus accumbens, the medial prefrontal cortex, and the basolateral amygdala. VTA DA neurons mediate stimuli saliency and goal-directed...

Moderate Stress-Induced Social Bonding and Oxytocin Signaling are Disrupted by Predator Odor in Male Rats

In times of stress, social support can serve as a potent buffering mechanism that enhances resilience. In humans, stress can promote protective affiliative interactions and prosocial behavior. Yet, stress also precipitates psychopathologies characterized by social withdrawal such as post-traumatic stress disorder (PTSD) and depression. The factors that drive adaptive vs...

Oral Cannabidiol does not Alter the Subjective, Reinforcing or Cardiovascular Effects of Smoked Cannabis

Cannabidiol (CBD), a constituent of cannabis with few psychoactive effects, has been reported in some studies to attenuate certain aspects of Δ9-tetrahydrocannabinol (THC) intoxication. However, most studies have tested only one dose of CBD in combination with one dose of oral THC, making it difficult to assess the nature of this interaction. Further, the effect of oral CBD on...

Architectural Representation of Valence in the Limbic System

In order to thrive, animals must be able to recognize aversive and appetitive stimuli within the environment and subsequently initiate appropriate behavioral responses. This assignment of positive or negative valence to a stimulus is a key feature of emotional processing, the neural substrates of which have been a topic of study for several decades. Until recently, the result of...

Reductions in Cortico-Striatal Hyperconnectivity Accompany Successful Treatment of Obsessive-Compulsive Disorder with Dorsomedial Prefrontal rTMS

Obsessive-compulsive disorder (OCD) is a disabling illness with high rates of nonresponse to conventional treatments. OCD pathophysiology is believed to involve abnormalities in cortico-striatal-thalamic-cortical circuits through regions such as dorsomedial prefrontal cortex (dmPFC) and ventral striatum. These regions may constitute therapeutic targets for neuromodulation...

Early Adverse Experiences and the Developing Brain

Children exposed to various forms of adversity early in life are at increased risk for a broad range of developmental difficulties, affecting both cognitive and emotional adjustment. We review a growing body of evidence suggesting that exposure to adverse circumstances affects the developing brain in ways that increase risk for a myriad of problems. We focus on two forms of...

Corticostriatal Afferents Modulate Responsiveness to Psychostimulant Drugs and Drug-Associated Stimuli

The medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) are both integral components of the corticobasal ganglia–thalamic circuitry that regulates addiction-related behaviors. However, the role of afferent inputs from mPFC to NAc in these behaviors is unclear. To address this, we used a Cre-recombinase-dependent viral vector approach to express Gi/o-coupled DREADDs...