Lysophosphatidic acid receptor-1: A protective receptor on alcoholism? Preclinical and clinical studies
Lysophosphatidic acid species (LPA) are lipid bioactive signaling molecules that have been recently implicated in the modulation of glial physiology and mielination, although recent studies linked them to neurogenesis, emotional responses and motivated behaviors. LPA species act through 5 different types of GPCR termed LPA1-5 r. Lysophosphatidic acid receptor 1 (LPA1r) is present in the central nervous system and it has been related with affective disorders including anxiety and depression-like behaviors. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Fernando Rodr íguez de Fonseca, Estela Castilla-Ortega, Francisco Javier Pavon, Nuria García-Marchena, Pedro Araos, Jose Luis Royo, Guillermo Estivill-Torrús, Luis Santín, Antonia Serrano Source Type: research
Phosphodiesterase type 7 inhibition: A novel mechanism for reduction of alcohol drinking and relapse to alcohol seeking
Phosphodiesterase 7 (PDE7) is a cyclic adenosine monophosphate (cAMP)-specific PDE encompassing two members, PDE7A and PDE7B. These enzymes are expressed in dopaminergic (DAergic) regions of the brain linked to addiction, such as nucleus accumbens (NAc) and ventral tegmental area (VTA). Combining behavioral, electrophysiological, and biochemical studies, we established a link between drug addiction and PDE7 function and demonstrated that selective inhibition of PDE7 impacts alcohol addiction. Specifically, using genetically selected alcohol preferring Marchigian Sardinian (msp) rats we demonstrated that PDE7 inhibitors (PD...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: George Gaitanaris, Gregory Demopulos, Roberto Ciccocioppo Source Type: research
Prefrontal cortex and cognitive and emotional deficits in alcohol use disorders
Alcohol use disorder patients show cognitive and emotional deficits. We performed structural and functional magnetic resonance imaging (MRI) and examined performance on a cognitive flexibility task (Intra- Extra-dimentional Set Shift and Reversal; IED) and an Emotional Facial Expression recognition task (EFE). Alcohol use disorder patients (n = 27) were less able than controls (n = 31) to change their behaviour in accordance with the changing of the rules in the IED and to recognise emotional expressions in faces. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: T. Duka Source Type: research
Bidirectional regulation of response strategy by cortico-accumbens projections
Alcohol use disorders are characterized by loss of the ability to control drug seeking and taking. This loss of cognitive control over actions can be modeled by investigating the transition from goal-directed actions to habitual behavior. Our findings suggest that chronic alcohol exposure promotes the development of inflexible habits, suggesting that chronic alcohol use itself may drive addictive behavior. Subregions of the prefrontal cortex have opposing roles in response strategy selection, such that prelimbic PFC is critically involved in the acquisition of goal-directed actions, while infralimbic PFC is necessary for t...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: J.M. Barker, K. Bryant, A. Montiel-Ramos, B. Goldwasser, L.J. Chandler Source Type: research
Altered communication of mPFC neuronal networks in postdependent rats state
Despite its limited immediate reinforcement value, alcohol has a potent ability to induce neuroadaptations that promote its increased incentive salience, escalation of voluntary alcohol intake and aversion resistant alcohol seeking. A constellation of these traits, collectively called “post-dependent”, emerges following brain exposure to repeated cycles of intoxication and withdrawal, and likely comprises a “relapse-prone” state of brain networks. We have demonstrated that the post-dependent syndrome in rats is associated with lasting reprogramming of transcriptional acti vity and function in the medial prefrontal ...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Wolfgang H. Sommer Source Type: research
How do we drink despite consequences: Exploring the hypothesis that the Insula instigates AUDs
Compulsive alcohol intake, where drinking continues despite negative social, legal and physical consequences, is a major obstacle to treating alcohol use disorders. There is particular interest in identifying circuits and molecules which drive compulsive intake, which could help develop novel therapeutic interventions. Activity in the anterior Insula cortex (aINS) during alcohol or drug cues predicts future intake and relapse in humans, and thus we hypothesize that aINS regulates activity across other brain regions, which together promotes compulsion. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Kelly Lei, Taban Seif, Jeffrey A. Simms, Scott Wegner, Bing Hu, Antonello Bonci, Robert O. Messing, F. Woodward Hopf Source Type: research
Chronic alcohol disrupts glutamatergic synaptic plasticity of hypothalamic parvocellular neurosecretory cells, and hormonal as well as behavioral responses to repeated stress
The chronic inability of alcoholics to effectively cope with relapse-inducing stressors has been linked to a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and corticotropin-releasing factor (CRF) signaling. However, the cellular mechanisms underlying the dysregulation of the HPA axis response to stress in alcohol dependence are yet to be identified. Using whole-cell patch-clamp recordings, we showed that stress induces a CRF-dependent depression of NMDAR function in parvocellular neurosecretory cells (PNCs) in the paraventricular nucleus of the hypothalamus (PVN), which allows for short-term potentiation (...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: V.N. Marty, Y. Mulpuri, D.H. Terry, M. Pempe ña, S. Yee, I. Spigelman Source Type: research
Interaction of CRF and kappa opioid systems on GABAergic neurotransmission in the mouse central amygdala
The corticotropin-releasing factor (CRF) and kappa-opioid receptor (KOR) systems are implicated in stress-related behaviors and drug dependence. Although previous studies suggest that antagonism of each system blocks aspects of experimental models of drug dependence, the possible interaction between these systems at the neuronal level has not been completely examined. We used an in vitro brain slice preparation to investigate the interaction of these two peptide systems on inhibitory neurotransmission in the central amygdala (CeA). (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Scott D. Moore Source Type: research
A distributed CRF network in rat extended amygdala regulates anxiety and excessive alcohol drinking
Corticotropin-releasing factor (CRF) is a central regulator of the stress response. Neurons that express CRF are particularly concentrated in the central amygdala (CeA), and bed nucleus of the stria terminalis (BNST). The role of CeA CRF neurons in anxiety remains controversial. To examine the role of CRF neurons in behavior, we generated a BAC transgenic Crh-Cre rat in which Cre recombinase is expressed from the Crh promoter. Cre+ neurons of these rats are immunoreactive for CRF and are clustered in the lateral CeA (CeL) and in dorsal BNST. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Robert O. Messing, Matthew B. Pomrenze, Giordano de Guglielmo, Marsida Kallupi, George F. Koob, Olivier George Source Type: research
Chronic alcohol-related neural and peripheral stress system dysfunction: Effects on alcohol craving, relapse and recovery
Chronic heavy alcohol use disrupts multilevel peripheral and brain adaptations in stress and homeostatic pathways but it is not clear which, if any, changes promote compulsive alcohol craving and relapse risk. Inpatient and outpatient early abstinent treatment engaged alcohol dependent (AD) patients and healthy social drinking controls were studied in separate laboratory and neuroimaging experiments in which their basal tonic and phasic stress and alcohol craving responses to acute stress, alcohol and neutral relaxing cues states were assessed. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Rajita Sinha Source Type: research
A novel human experimental model of stress-induced alcohol self-administration in binge and non-binge drinkers
Studies show that craving and physiological responses to cues mimicking real-world alcohol and stress triggers can predict relapse to alcohol use in alcohol-dependent individuals. The association between this cue reactivity and alcohol consumption in non-dependent drinkers is less clear. Our objective was to characterize acute stress and alcohol-cue reactivity, using guided-imaging scripts, and their relationship to craving and IV alcohol self-administration (IV-ASA) in non-dependent drinkers. Participants (N = 23) included non-dependent binge and non-binge drinkers that completed three experimental IV-ASA sessions. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Bethany L. Stangl, Laura Kwako, Rajita Sinha, Vijay A. Ramchandani Source Type: research
Binge-heavy alcohol alters cortisol and subjective craving: Impact on compulsive alcohol motivation and intake
In this study, we examined whether alcohol-related neuroendocrine adaptations drive compulsive alcohol motivation and intake in moderate, non-binging (MD) and binge/heavy (BH) non-smoking social drinkers who participated in an experiment that measured the specific effects of stress, alcohol cue, and neutral cue exposure, followed by discrete alcohol cues, on neuroendocrine function, subjective alcohol craving, and behavioral alcohol motivation and intake. The “alcohol taste test” (ATT) was used as an implicit measure of behavioral alcohol motivation and intake. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: S. Blaine, D. Seo, R. Sinha Source Type: research
Gender differences in how stress affects intravenous alcohol administration
Gender differences on the association of stress and drinking exist, but few studies have examined this phenomenon using alcohol self-administration (ASA) paradigms in humans. We recently investigated such differences in ASA in the laboratory after 2 distinct stress-inducing experiences. First, we examined operant responding for alcohol after a negative mood-induction priming exercise. Second, we modeled a human analogue of the alcohol deprivation effect. In the mood-induction study 34 (19 women) participants (mean 24.9 years, SD 3.4) completed 2 intravenous ASA sessions: under either negative or neutral mood. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: M.H. Plawecki, M.A. Cyders, K. White, J.S. Vanderveen, A. Kosobud, V. Vitvitskiy, N. Grahame, J. Millward, J. Haines, J. Hays, S. Shehkar, J.N. Nurnberger, D. Kareken, D. Crabb, S.J. O'Connor Source Type: research
Childhood trauma in alcohol dependence: Vulnerability and relative resilience
In this study, we identify and characterize individuals exposed to severe childhood trauma as either “vulnerable” or “resilient” to risk for AD. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Melanie L. Schwandt, Markus Heilig, David T. George, Dan Hommer, Vijay A. Ramchandani Source Type: research
Integrative analysis of human and non-human primate brain tissue for alcohol consumption
Alcohol abuse is a significant worldwide socioeconomic problem. Unbiased systems-based approaches assist in the identification of causal mechanisms for the manifestation, progression, and maintenance of disease. An in-depth RNA-Seq study of human and rhesus macaque central amygdala (CEA), a brain region with known involvement in stress and addiction, was conducted to facilitate discovery of novel genes and gene networks underlying lifetime alcohol consumption. The number of genes expressed within postmortem human brain samples was comparable to those genes reliable detected in macaques, allowing a comprehensive parallel ex...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Sean P. Farris, Ovidiu Iancu, Robert Hitzemann, Kathy Grant, Nicole A.R. Walter, R. Adron Harris, R. Dayne Mayfield Source Type: research
