Circuit dynamics of in vivo dynorphn release in the nucleus accumbens
We recently used an optogenetic approach to demonstrate that stimulation of dynorphinergic cells in the ventral nucleus accumbens shell (vNAcSh) elicits robust aversive behavior and photostimulation of dorsal NAcSh dynorphin (dNAcSh) cells induces a place preference and is positively reinforcing. Both of which appear to be dependent on kappa opioid receptor (KOR) activation. To follow these recently published findings, we are investigating how KOR is able to mediate these opposing behaviors in two distinct regions of the NAcSh. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Ream Al-Hasani, Jenny M. Wong, Jordan G. McCall, Omar S. Mabrouk, Gavin Schmitz, Kirsten Porter-Stransky, Julio M. Bernardi, Brandon Aragona, Robert T. Kennedy, Michael R. Bruchas Source Type: research
Neuroimmune regulation of alcohol consumption
Molecular and behavioral studies suggest a role for the innate immune system in the acute and chronic effects of alcohol and support a neuroimmune hypothesis of alcohol addiction. Changes in expression of immune-related genes and microglial transcripts occur in postmortem brains from alcoholics and animals exposed to alcohol, and mutant animals lacking certain innate immune genes show decreased alcohol-mediated responses. Many of the differentially expressed genes are part of the Toll-like receptor (TLR) pathway that culminates in increased expression of proinflammatory cytokines. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: R. Adron Harris, Anna S. Warden, R. Dayne Mayfield, Yuri A. Blednov Source Type: research
Gender differences in alcohol-induced immune response in human and animal adolescents with binge drinking: Role of TLR4
Adolescent stress response and coping strategies differ to that of adults. Heavy binge drinking in adolescence is the most frequent pattern of drinking among teenagers. Experimental evidence indicates the participation of the immune system and TLR4 response in the ethanol-induced adolescent brain damage and the vulnerability of the female vs males. We assess the plasma cytokine and chemokine levels in male and female adolescents during acute alcohol intoxication, and correlate these results with the TLR4 response. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Mar ía Pascual, Jorge Montesinos, Miguel Marcos, Francisco-Javier Laso, Consuelo Guerri Source Type: research
NLRP3/ASC inflammasome activation and micro-RNA-155 contribute to alcohol-induced neuroinflammation
Alcohol-induced neuroinflammation is mediated by pro-inflammatory cytokines including interleukin-1-beta (IL-1 β). IL-1β production requires caspase-1 activation by inflammasomes, multiprotein complexes that are assembled in response to danger signals. We hypothesized that alcohol-induced inflammasome activation contributes to increased IL-1β in the brain. We found increased expression of inflammasome com ponents (NLRP1, NLRP3, ASC) and pro-inflammatory cytokines (TNFα, MCP-1) in the brain of alcohol-fed compared to control mice. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Gyongyi Szabo, Dora Lippai, Shashi Bala Source Type: research
Toll-like receptors, alcohol and stress-induced changes in neurobiology
Ethanol increases expression of innate immune genes that contribute to the development of alcoholic pathology. Innate immune genes induced by binge drinking include HMGB1, multiple Toll-like receptors(TLR), RAGE, multiple cytokines, and chemokines that are increased in blood, liver and brain. Ethanol induction of TLR and neuroimmune genes involves ethanol-induced release of HMGB1 that stimulates and induces TLR-increasing NFkB-DNA binding and transcription of CCL2, TNFalpha, RAGE and other target genes. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: F.T. Crews, R. Vetreno, V. Massey, L. Qin, L. Coleman, J. Zou Source Type: research
Traumatic stress effects on brain CRFR1 signaling, nociception & alcohol drinking
Some (but not all) humans exposed to traumatic stress develop post-traumatic stress disorder (PTSD), which is defined by high avoidance of trauma-related stimuli, hyperarousal, and negative affect, and which is highly co-morbid with Alcohol Use Disorder (AUD). Our lab utilizes a stress model in which rats are indexed for avoidance of a predator odor-paired context, and divided into “Avoiders” (i.e., high stress reactivity) and “Non-Avoiders” (i.e., low stress reactivity). Previous work by our lab showed that Avoiders exhibit persistent increases in alcohol drinking and altered prefrontal cortex (PFC)-amygdala neuro...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Nicholas W. Gilpin Source Type: research
Exacerbation of the inherent “anxiety” state by unpredictability of alcohol access in Sardinian alcohol-preferring rats
At the last two Volterra meetings this lab has contributed several sets of data on a new experimental procedure of alcohol intake capable of promoting binge-like drinking in selectively bred, Sardinian alcohol-preferring (sP) rats. Specifically, exposure of sP rats to multiple alcohol concentrations (10%, 20%, and 30%, v/v), under the 4-bottle “alcohol vs water” choice regimen, in daily 1-hour drinking sessions with an unpredictable time schedule, resulted in intoxicating intakes of alcohol (≥2 g/kg; BALs≥100 mg%) when the drinking session occurred over the final hours of the dark phase of the light/dark cycle. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Giancarlo Colombo, Carla Lobina, Irene Lorrai, Paola Maccioni, Gian Luigi Gessa Source Type: research
Adolescent social isolation as a rodent model of heightened vulnerability to comorbid anxiety/stressor-related disorders and alcoholism
Although anxiety/stressor-related disorders and alcoholism frequently co-occur, the neural substrates underlying this comorbidity are unclear. To address this gap in our knowledge, we have characterized a rodent adolescent social isolation (aSI) model and shown that it elicits robust, long-lasting alterations in many behavioral risk factors for anxiety disorders or alcoholism, including increases in anxiety-like behaviors, deficits in fear extinction, and escalated ethanol intake. We are now using this model to identify neural substrates that contribute to the “anxiety/addiction vulnerable” phenotype engendered by this...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Jeff L. Weiner Source Type: research
Genetic and neural correlates of stress-related psychiatric disorders and alcoholism
The genetic and neural substrates underlying the comorbidity between stress-related psychiatric disorders (e.g., depression, anxiety disorders) and alcoholism remain poorly understood. I will show that polygenic risk for stress-related internalizing disorders is shared with risk for alcohol dependence (N = 2773 as well as ongoing PGC work). Further, I will present evidence from a large ongoing neuroimaging study of college students (N = 1332) that reward-related ventral striatum (VS) function has a quadratic relationship with problematic alcohol use wherein both relatively low and high VS react ivity is associated wit...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Ryan Bogdan Source Type: research
A chimeric approach to evaluate the role of corticotropin releasing factor in alcohol use disorder
The corticotropin releasing factor (CRF) exerts its effects by acting on its receptors and on the binding protein (CRFBP), and has been implicated in alcohol use disorder (AUD). Therefore, identification of the exact contribution of each protein that mediates CRF effects is necessary to design effective therapeutic strategies for AUD. A series of in vitro chimeric experiments using CRF-receptor 2 (CRFR2) and CRFBP were performed to define the allosteric modulation of CRF on CRFR2. First, to establish the CRFBP role in receptor signaling, we developed a novel chimeric cell-based assay and showed that that CFRBP full length ...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Carolina L. Haass-Koffler, Andrea T. Henry, Gerd Melkus, Jeffrey A. Simms, Mohammed Naemmuddin, Carsten K. Nielsen, Amy W. Lasek, Molly Magill, Melanie L. Schwandt, Reza Momenan, Colin A. Hodgkinson, Selena E. Bartlett, Robert M. Swift, Antonello Bonci, L Source Type: research
Inputs from the medial prefrontal cortex to the rostromedial tegmental nucleus are involved in signaling the aversive properties of alcohol
The recent discovery of the rostromedial tegmental nucleus (RMTg), a midbrain region that exerts inhibitory control over dopamine and is involved in aversive responding, has sparked renewed interest in the neurobiology of aversion and its role in addiction. To investigate the RMTg ’s role in signaling the aversive properties of alcohol, we measured cFos induction following conditioned taste aversion (CTA) and found that expression was significantly enhanced in the RMTg following exposure to a conditioned stimulus predictive of ethanol exposure (p ≤ 0.01). (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Elizabeth J. Glover, E. Margaret Starr, Molly J. McDougle, Thomas C. Jhou, L. Judson Chandler Source Type: research
A thalamo-limbic neuropeptide circuit driving binge drinking behavior
Repeated cycles of binge drinking and withdrawal drive subsequent alcohol consumption that leads to alcohol dependence and mood disorders, so characterizing the neural circuitry underlying this risky behavior is essential to treating alcohol use disorders. We recently showed that neurons that produce the endogenous stress peptide corticotropin-releasing factor (CRF) within the bed nucleus of the stria terminalis (BNST) promote binge-like alcohol drinking and anxiety in mice, however the excitatory inputs that drive BNST CRF neuron activity to promote these behaviors have yet to be characterized. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: K.E. Pleil, J.F. DiBerto, A.M. Kendra, A. Shirke, S. Chien, T.L. Kash Source Type: research
Adolescent stress-induced social anxiety: A role for basolateral amygdala kappa opioid receptors
Adolescence is a developmental period marked by robust neural alterations and heightened vulnerability to stress, a factor that is highly associated with increased risk for emotional processing deficits, such as anxiety. Stress-induced upregulation of the dynorphin/kappa opioid receptor (DYN/KOR) system is thought to underlie the negative affect associated with stress. The basolateral amygdala (BLA) is a key structure involved in anxiety, and neuromodulatory systems, such as the DYN/KOR system, can 1) regulate BLA neural activity in an age-dependent manner in stress-na ïve animals and 2) underlie stress-induced anxiety in...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: J. Herman, E. Varlinskaya, T. Deak, M.R. Diaz Source Type: research
Differential tonic inhibition and ethanol effects in the central and lateral amygdala corticotropin releasing factor receptor 1 (CRF1) circuitry
Despite the prevalence of alcohol dependence, the underlying neurobiological mechanisms remain unclear. My research focuses on changes in inhibitory control of corticotropin releasing factor receptor 1 (CRF1) neurons in the central (CeA) and lateral amygdala (LA). Amygdalar CRF1 has been implicated in neuroplastic changes related to fear, anxiety, and alcohol. Using a transgenic mouse model expressing green fluorescent protein (GFP) in neurons containing CRF1, we examined inhibitory transmission and ethanol sensitivity in CRF1-containing (CRF1+) and unlabeled (CRF1-) CeA and LA neurons. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Melissa A. Herman Source Type: research
Regulation of NMDA receptors and plasticity in the BNST following adolescent alcohol exposure
Adolescent alcohol use is one of the strongest predictors for future alcohol dependence. In animal models, adolescent alcohol exposure produces long-term changes in a number of brain regions. The long-term adaptations in areas of the brain involved in processing stress may be key due to the importance of stress to relapse. The bed nucleus of the stria terminalis, BNST, is one of these regions. In the adult BNST, these long-term adaptations or plasticity produced by alcohol are primarily regulated by NMDA receptors, especially those containing the GluN2B subunit. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: M.C. Miller, N.M. Sharfman, J.R. Grant, S.D. Fox, T.A. Wills Source Type: research
