Generalized cue reactivity in rat dopamine neurons after opioids.

Cue reactivity is the maladaptive neurobiological and behavioral response upon exposure to drug cues and is a major driver of relapse. A widely accepted assumption is that drugs of abuse result in disparate dopamine responses to cues that predict drug vs. natural rewards.

Associations of Mild Behavioral Impairment Domains with Brain Volumes: Cross-sectional Analysis of Atherosclerosis Risk in Community (ARIC) Study.

Background: Mild behavioral impairment (MBI) has been associated with global brain atrophy, but the regional neural correlates of MBI symptoms are less clear, particularly among community-dwelling older individuals without dementia.

Objective: Our objective was to examine the associations of MBI domains with gray matter (GM) volumes in a large population-based sample of older adults without dementia.

Methods: We performed a cross-sectional study of 1445 community-dwelling older adults in the Atherosclerosis Risk in Communities Study who underwent detailed neurocognitive assessment and brain magnetic resonance imaging in 2011-2013.

Transcranial Focused Ultrasound Neuromodulation in Psychiatry: Main Characteristics, Current Evidence, and Future Directions.

Non-invasive brain stimulation (NIBS) techniques are designed to precisely and selectively target specific brain regions, thus enabling focused modulation of neural activity. Among NIBS technologies, low-intensity transcranial focused ultrasound (tFUS) has emerged as a promising new modality. The application of tFUS can safely and non-invasively stimulate deep brain structures with millimetric precision, offering distinct advantages in terms of accessibility to non-cortical regions over other NIBS methods.

Generalized cue reactivity in dopamine neurons after opioids.

Cue reactivity is the maladaptive neurobiological and behavioral response upon exposure to drug cues and is a major driver of relapse. The leading hypothesis is that dopamine release by addictive drugs represents a persistently positive reward prediction error that causes runaway enhancement of dopamine responses to drug cues, leading to their pathological overvaluation compared to non-drug reward alternatives. However, this hypothesis has not been directly tested.

Opioid modulation of prefrontal cortex cells and circuits.

Several neurochemical systems converge in the prefrontal cortex (PFC) to regulate cognitive and motivated behaviors. A rich network of endogenous opioid peptides and receptors spans multiple PFC cell types and circuits, and this extensive opioid system has emerged as a key substrate underlying reward, motivation, affective behaviors, and adaptations to stress. Here, we review the current evidence for dysregulated cortical opioid signaling in the pathogenesis of psychiatric disorders.

Stable, neuron-specific gene expression in the mouse brain.

Gene delivery to, and expression in, the mouse brain is important for understanding gene functions in brain development and disease, or testing gene therapies. Here, we describe an approach to express a transgene in the mouse brain in a cell-type-specific manner. We use stereotaxic injection of a transgene-expressing adeno-associated virus into the mouse brain via the intracerebroventricular route.

Brain lesions disrupting addiction map to a common human brain circuit.

Drug addiction is a public health crisis for which new treatments are urgently needed. In rare cases, regional brain damage can lead to addiction remission. These cases may be used to identify therapeutic targets for neuromodulation.

Deep brain stimulation effect on anterior pallidum reduces motor impulsivity in Parkinson's disease.

Background: Deep Brain Stimulation (DBS) of the subthalamic nucleus or globus pallidus internus is used to treat the motor symptoms of Parkinson's disease. The former can worsen impulsive and compulsive behaviors after controlling for the reduction of dopaminergic medications. However, the effect of pallidal DBS on such behaviors in PD patients is less clear.

Operant Vapor Self-administration in Mice.

Models of drug addiction in rodents are instrumental in understanding the underlying neurobiology. Intravenous self-administration of drugs in mice is currently the most commonly used model; however, several challenges exist due to complications related to catheter patency. To take full advantage of the genetic tools available to study opioid addiction in mice, we developed a non-invasive mouse model of opioid self-administration using vaporized fentanyl.

Excitation of medium spiny neurons by 'inhibitory' ultrapotent chemogenetics via shifts in chloride reversal potential.

Ultrapotent chemogenetics, including the chloride-permeable inhibitory PSAM-GlyR receptor, were recently proposed as a powerful strategy to selectively control neuronal activity in awake, behaving animals. We aimed to validate the inhibitory function of PSAM-GlyR in dopamine D1 receptor-expressing medium spiny neurons (D1-MSNs) in the ventral striatum. Activation of PSAM-GlyR with the uPSEM ligand enhanced rather than suppressed the activity of D1-MSNs in vivo as indicated by increased c-fos expression in D1-MSNs and in vitro as indicated by cell-attached recordings from D1-MSNs in mouse brain slices.

A 33-Year-Old Man with Progressive Diffuse and Focal Neuropsychiatric Signs without Localizing Correlates on Brain Imaging: A Systematic Approach to Diagnosis.

Introduction: Novel expensive diagnostic tests are rapidly emerging. However, the answer to the most complex clinical presentations is often inferred from a systematic approach to the differential diagnosis. This is especially the case in neuropsychiatric disorders that present with a mix of neurologic and psychiatric symptoms.

Paraneoplastic PRES from lymphoma induced hypercalcemia: Case report and review of the literature.

Hypercalcemia from tumors has been associated with Posterior Reversible Encephalopathy Syndrome (PRES) but the mechanism remains unclear. In this article, we describe a case of PRES caused by hypercalcemia from lymphoma. We summarize the available scientific evidence linking hypercalcemia to failure of cerebral autoregulation and potentially PRES.

Brainstem and limbic encephalitis with paraneoplastic neuromyelitis optica.

The spectrum of disorders associated with anti-neuromyelitis optica (NMO) antibody is being extended to include infrequent instances associated with cancer. We describe a patient with brainstem and limbic encephalitis from NMO-immunoglobulin G in serum and cerebrospinal fluid in the context of newly diagnosed breast cancer. The neurological features markedly improved with excision of her breast cancer and immune suppressive therapy.

Optogenetic inhibition of cocaine seeking in rats.

Inhibitory optogenetics was used to examine the roles of the prelimbic cortex (PL), the nucleus accumbens core (NAcore) and the PL projections to the NAcore in the reinstatement of cocaine seeking. Rats were microinjected into the PL or NAcore with an adeno-associated virus containing halorhodopsin or archaerhodopsin. After 12 days of cocaine self-administration, followed by extinction training, animals underwent reinstatement testing along with the presence/absence of optically induced inhibition via laser light.

Role of mGluR5 neurotransmission in reinstated cocaine-seeking.

In animal models of addiction, reducing glutamate stimulation of the metabotropic glutamate receptor 5 (mGluR5) inhibits drug-seeking. The present study used the reinstatement model of cocaine-seeking to show that blockade of mGluR5 directly in the core subcompartment of the nucleus accumbens (NAcore) prevented both conditioned cue- and cocaine-reinstated drug-seeking. Consistent with this finding, microinjection of the mGluR5 agonist (RS)-2-chloro-5-hydroxyphenylglycine into the NAcore produced modest reinstatement of lever pressing when given alone and significantly potentiated cue-induced reinstatement.

Extracellular glutamate: functional compartments operate in different concentration ranges.

Extracellular glutamate of glial origin modulates glial and neuronal glutamate release and synaptic plasticity. Estimates of the tonic basal concentration of extracellular glutamate range over three orders of magnitude (0.02-20 μM) depending on the technology employed to make the measurement.