Rates and correlates of antiretroviral therapy use and virologic suppression among perinatally and behaviorally HIV-infected youth linked to care in the United States.

Objective: To measure rates of antiretroviral therapy (ART) use and virologic suppression among perinatally HIV-infected youth (PIY) and behaviorally HIV-infected youth (BIY) linked to care in the United States and examine the effects of demographic, biomedical, and psychosocial factors on those rates.

Methods: Between 2009 and 2012, 649 PIY and 1547 BIY in 20 Adolescent Medicine Trials Network for HIV/AIDS Interventions sites completed cross-sectional surveys through audio computer-assisted self-interviews. Viral load data were collected from chart abstraction or blood draw.

Critical role of peripheral vasoconstriction in fatal brain hyperthermia induced by MDMA (Ecstasy) under conditions that mimic human drug use.

MDMA (Ecstasy) is an illicit drug used by young adults at hot, crowed "rave" parties, yet the data on potential health hazards of its abuse remain controversial. Here, we examined the effect of MDMA on temperature homeostasis in male rats under standard laboratory conditions and under conditions that simulate drug use in humans. We chronically implanted thermocouple microsensors in the nucleus accumbens (a brain reward area), temporal muscle, and facial skin to measure temperature continuously from freely moving rats.

Role of nucleus accumbens shell neuronal ensembles in context-induced reinstatement of cocaine-seeking.

Environmental contexts previously associated with drug use provoke relapse to drug use in humans and reinstatement of drug seeking in animal models of drug relapse. We examined whether context-induced reinstatement of cocaine seeking is mediated by activation of context-selected nucleus accumbens neurons. We trained rats to self-administer cocaine in Context A and extinguished their lever-pressing in a distinct Context B.

Molecular neuroanatomy: a generation of progress.

The neuroscience research landscape has changed dramatically over the past decade. Specifically, an impressive array of new tools and technologies have been generated, including but not limited to: brain gene expression atlases, genetically encoded proteins to monitor and manipulate neuronal activity, and new methods for imaging and mapping circuits. However, despite these technological advances, several significant challenges must be overcome to enable a better understanding of brain function and to develop cell type-targeted therapeutics to treat brain disorders.

New technologies for examining the role of neuronal ensembles in drug addiction and fear.

Correlational data suggest that learned associations are encoded within neuronal ensembles. However, it has been difficult to prove that neuronal ensembles mediate learned behaviours because traditional pharmacological and lesion methods, and even newer cell type-specific methods, affect both activated and non-activated neurons. In addition, previous studies on synaptic and molecular alterations induced by learning did not distinguish between behaviourally activated and non-activated neurons.

Role of orbitofrontal cortex neuronal ensembles in the expression of incubation of heroin craving.

In humans, exposure to cues previously associated with heroin use often provokes relapse after prolonged withdrawal periods. In rats, cue-induced heroin seeking progressively increases after withdrawal (incubation of heroin craving). Here, we examined the role of orbitofrontal cortex (OFC) neuronal ensembles in the enhanced response to heroin cues after prolonged withdrawal or the expression of incubation of heroin craving.

FACS identifies unique cocaine-induced gene regulation in selectively activated adult striatal neurons.

Numerous studies with the neural activity marker Fos indicate that cocaine activates only a small proportion of sparsely distributed striatal neurons. Until now, efficient methods were not available to assess neuroadaptations induced specifically within these activated neurons. We used fluorescence-activated cell sorting (FACS) to purify striatal neurons activated during cocaine-induced locomotion in naive and cocaine-sensitized cfos-lacZ transgenic rats.

Methamphetamine-induced dopamine-independent alterations in striatal gene expression in the 6-hydroxydopamine hemiparkinsonian rats.

Unilateral injections of 6-hydroxydopamine into the medial forebrain bundle are used extensively as a model of Parkinson's disease. The present experiments sought to identify genes that were affected in the dopamine (DA)-denervated striatum after 6-hydroxydopamine-induced destruction of the nigrostriatal dopaminergic pathway in the rat. We also examined whether a single injection of methamphetamine (METH) (2.

Long-term upregulation of protein kinase A and adenylate cyclase levels in human smokers.

Repeated injections of cocaine and morphine in laboratory rats cause a variety of molecular neuroadaptations in the cAMP signaling pathway in nucleus accumbens and ventral tegmental area. Here we report similar neuroadaptations in postmortem tissue from the brains of human smokers and former smokers. Activity levels of two major components of cAMP signaling, cAMP-dependent protein kinase A (PKA) and adenylate cyclase, were abnormally elevated in nucleus accumbens of smokers and in ventral midbrain dopaminergic region of both smokers and former smokers.

Protein kinase A activation down-regulates, whereas extracellular signal-regulated kinase activation up-regulates sigma-1 receptors in B-104 cells: Implication for neuroplasticity.

The sigma-1 receptor (Sig-1R) can bind psychostimulants and was shown to be up-regulated in the brain of methamphetamine self-administering rats. Up-regulation of Sig-1Rs has been implicated in neuroplasticity. However, the mechanism(s) whereby Sig-1Rs are up-regulated by psychostimulants is unknown.

Prevalence, correlates, and comorbidity of DSM-IV antisocial personality syndromes and alcohol and specific drug use disorders in the United States: results from the national epidemiologic survey on alcohol and related conditions.

Objective: The purpose of this study was to provide nationally representative data on the prevalence, sociodemographic correlates, and comorbidity of antisocial syndromes across alcohol and 8 specific drug use disorders, including sedative, tranquilizer, opiate, stimulant, hallucinogen, cannabis, cocaine, and inhalant/solvent abuse and dependence.

Method: This study is based on a nationally representative sample of adults. Lifetime prevalences of antisocial syndromes were estimated and logistic regression analyses were used to examine associations between antisocial syndromes and sociodemographic characteristics and substance use disorders.

Patient and program factors in obtaining supportive services in DATOS.

This study examined patient and program factors that influenced the receipt of scheduled supportive services in the Drug Abuse Treatment Outcome Studies (DATOS). Patients (N = 2,932) in 21 long-term residential (LTR) programs, 27 outpatient methadone treatment (OMT), and 25 outpatient drug-free programs were interviewed at admission and at 3 months during treatment. A hierarchical regression analysis was used to examine the relationship between patient-level and program-level factors associated with receiving supportive services in seven categories (medical, psychological, family, legal, educational, vocational, and financial).

Molecular neuroadaptations in the accumbens and ventral tegmental area during the first 90 days of forced abstinence from cocaine self-administration in rats.

Cocaine self-administration is associated with a propensity to relapse in humans and reinstatement of drug seeking in rats after prolonged withdrawal periods. These behaviors are hypothesized to be mediated by molecular neuroadaptations within the mesolimbic dopamine system. However, in most studies of drug-induced neuroadaptations, cocaine was experimenter-delivered and molecular measurements were performed after short withdrawal periods.

A factor analysis of the Fagerström Test for Nicotine Dependence (FTND).

Psychometric study of the Fagerström Test for Nicotine Dependence (FTND) provides insight into its structure and the dimensions of nicotine addiction it assesses. We evaluated the factor structure of the FTND in 541 research volunteers, most with histories of polysubstance use. Tetrachoric and phi correlation techniques were utilized and promax- and varimax-rotated solutions are reported.

Time-dependent increases in brain-derived neurotrophic factor protein levels within the mesolimbic dopamine system after withdrawal from cocaine: implications for incubation of cocaine craving.

Using a rat model of drug craving, we found that the responsiveness to cocaine cues progressively increases or incubates over the first 60 d of cocaine withdrawal. Here we studied whether alterations in brain-derived neurotrophic factor (BDNF) protein levels within the mesolimbic dopamine system are associated with this incubation phenomenon. BDNF is involved in synaptic plasticity and was found to enhance responding for cues associated with natural rewards.

Regulating ankyrin dynamics: Roles of sigma-1 receptors.

Ankyrin is a cytoskeletal adaptor protein that controls important cellular functions, including Ca(2+) efflux at inositol 1,4,5-trisphosphate receptors (IP(3)R) on the endoplasmic reticulum. The present study found that sigma-1 receptors (Sig-1R), unique endoplasmic reticulum proteins that bind certain steroids, neuroleptics, and psychotropic drugs, form a trimeric complex with ankyrin B and IP(3)R type 3 (IP(3)R-3) in NG-108 cells. The trimeric complex could be coimmunoprecipitated by antibodies against any of the three proteins.

D2 dopamine receptor gene TaqI A1 and B1 restriction fragment length polymorphisms: enhanced frequencies in psychostimulant-preferring polysubstance abusers.

Several lines of evidence suggest that presence of a D2 dopamine receptor (DRD2) gene variant marked by TaqI restriction fragment length polymorphisms (RFLPs) might contribute to vulnerability to substance abuse. Psychostimulants display the most robust enhancement of dopamine activity in mesolimbic/mesocortical circuits important for behavioral reward. The present study tests the hypothesis that a DRD2 gene variant might be more prominent in polysubstance users who preferentially use psychostimulants than in addicts with preferential opiate use or in those with no drug preference.