Optogenetic characterization of CeA CRF pathways in alcohol dependence
In alcohol dependent animals, withdrawal from alcohol activates a subpopulation of neurons within the central nucleus of amygdala (CeA) and produces high levels of alcohol consumption. However, the phenotype of the neurons activated, the causal role of these neurons, and the specific downstream pathways responsible for these effects are poorly known. We used Crh-Cre transgenic rats combined with in vivo optogenetics to test if the inactivation of CeA CRF neurons or CRF terminals in downstream regions prevents excessive alcohol self-administration during withdrawal. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Giordano de Guglielmo, Marsida Kallupi, Elena Crawford, George F. Koob, Robert O. Messing, Olivier George Source Type: research
Cortical and thalamic inputs to the nucleus accumbens bi-directionally modulate ethanol consumption in C57BL/6J mice
The infralimbic cortex (IL) and anterior paraventricular nucleus of the thalamus (aPVT) provide glutamatergic input to the NAc shell and excitation or inhibition of these pathways may modulate ethanol-drinking behavior. Using a chemogenetic approach, we examined the role of these brain regions on basal ethanol intake. AAV viruses containing hM3Dq-CaMKII-mCherry DREADDs were infused into the IL or aPVT and bilateral microinjection guide cannula were positioned over the NAc in C57BL/6J mice. After training mice to drink ethanol using a modified drinking in the dark paradigm, mice were challenged with systemic 3mg/kg clozapin...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: H.L. Haun, R. Cannady, P.J. Mulholland, W.C. Griffin, H.C. Becker Source Type: research
Rapid antidepressant synapse formation requires GABAB receptor-activation of mTORC1
Similar to rapid antidepressants, ethanol blocks N-methyl-D-aspartate glutamate receptors (NMDAR) and activates the mammalian target of rapamycin (mTOR). Additionally, moderate alcohol consumption has been demonstrated to affect synaptic connections. Our lab has previously demonstrated that the administration of NMDAR antagonists causes a functional shift in metabotropic gamma-aminobutyric acid (GABA) receptors (GABABRs). This shift decreases the coupling of GABABRs to potassium channels and instead promotes coupling to calcium channels. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Chelcie F. Heaney, Emily R. Workman, Emma K. Ericsson, Kimberly F. Raab-Graham Source Type: research
Estrogen enhances ethanol and dopamine effects on ventral tegmental neurons from female mice
Gender differences in alcohol use disorder may be modulated by steroid hormones such as estrogen. Estradiol, the predominant circulating form of estrogen in pre-menopausal females, increases binge-like drinking and enhances ethanol conditioned place preference in mice, suggesting that estradiol affects the rewarding properties of ethanol. The ventral tegmental area (VTA) is involved in reward and reinforcement in addiction. To determine whether estrogen affects VTA neuronal physiology, freely cycling female and ovariectomized (OVX) mice supplemented with estradiol benzoate (EB) were used for brain slice electrophysiologica...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: B.J. Vandegrift, C. You, R. Satta, M.S. Brodie, A.W. Lasek Source Type: research
Family history of problematic alcohol use, stress, and delay discounting: A moderated mediation analysis
Background: Positive family history of problematic alcohol use is implicated in impulsive behavior, poor response to stress, and alcohol problems. However, the specific nature of these associations is unclear. Method: Participants were 393 undergraduate college students who reported heavy episodic drinking and were part of a brief intervention trial. Analyses were conducted with pre-intervention baseline data. Measures included family history of problematic alcohol use, delay discounting (impulsivity), levels of stress, typical weekly drinks, and past month alcohol-related problems. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Lidia Z. Meshesha, Matthew Martens, James G. Murphy Source Type: research
Paradoxical effects of the cortisol response to stress: More cravings now, less alcohol use later
Introduction: Glucocorticoids, cortisol in humans, might be critically involved in the individual propensity for addictions. By inducing social stress in young healthy males, the putative mediating role of cortisol was investigated in immediate cravings for alcohol, and in alcohol use at the long term. Methods: In an experimental prospective design, 107 young healthy males randomly received acute social stress using the Trier Social Stress Test (TSST) or a control condition. Next, subliminal alcohol pictures were shown in the fMRI scanner. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Nicole Y.L. Oei, Reinout W. Wiers Source Type: research
Cortical integration of chronic stress and alcohol dependence: A possible role for KCa2 channels
Alcohol dependence produces altered responses to stress, which may further exacerbate excessive drinking. Growing evidence suggests small-conductance Ca2+-activated K+ (KCa2) channels have the ability to protect against anxiety and stress-related behaviors. Pharmacological manipulation or genetic depletion of KCa2 channels alters forced swim stress behavior and ethanol consumption after chronic stress exposure. Chronic exposure to forced swim stress (FSS), results in a stress-induced enhancement of voluntary ethanol consumption in mice with a history of alcohol exposure. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Audrey E. Padula, Reginald Cannady, Marcelo F. Lopez, Howard C. Becker, Patrick J. Mulholland Source Type: research
Dysregulation of hippocampal and frontocortical JNK signaling in alcohol dependence
Alcohol dependence is a chronic, relapsing psychiatric disorder characterized by the emergence of negative emotional states and the development of significant pain hypersensitivity (or hyperalgesia) during withdrawal. Accordingly, alcohol may be sought after and taken in excessive amounts to alleviate withdrawal-related symptoms. To develop more effective therapeutic treatments for dependence it is necessary to identify potential molecular targets that underlie the transition to excessive drinking. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Amanda R. Pahng, Rod I. Paulsen, Muhammad A. Farooq, Kimberly N. Edwards, Scott Edwards Source Type: research
Evaluation of plasma chemokines in patients with alcohol use disorders: Association of CCL11 (Eotaxin-1) with comorbid mental disorders
This study intends to evaluate the plasma chemokine concentrations in women and men with alcohol use disorders (AUD) and associated psychiatric comorbidity. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: N. Garc ía-Marchena, P. Araos, V. Barrios, L. Sanchez-Marin, J.A. Chowen, G. Ponce, J. Argente, G. Rubio, A. Serrano, F. Rodríguez de Fonseca, F.J. Pavon Source Type: research
Racial differences in stress-induced HPA reactivity in alcohol-dependent men
This study sought to identify racial differences in HPA dysregulation among persons with alcohol dependence. Twenty-six controls (18 Caucasian) and sixty-seven 4 to 6 week abstinent participants with alcohol dependence (52 Caucasian) completed a Trier Social Stress Task with two blood draws preceding and six over the following hour. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: J.L. Price, I.R. Frazier, M.A. Javors, R. Walker, U. Rao, S.J. Nixon, B. Adinoff Source Type: research
Changes in anxiety-like behavior and CRF gene expression in the basolateral amygdala of Lim-domain-only 3 (Lmo3) knockout mice
The LIM-domain only protein LMO3 is a transcriptional regulator that we have shown regulates behavioral responses to alcohol. Specifically, Lmo3 knockout (Lmo3KO) mice exhibit increased ethanol consumption, enhanced ethanol-induced sedation, and altered cocaine and ethanol reward. Due to the high comorbidity of alcohol use and anxiety, we investigated anxiety-like behavior in Lmo3KO mice using the elevated plus maze (EPM) and novelty-induced hypophagia tasks. We next explored the mechanism by which LMO3 may be regulating anxiety by measuring expression levels of CRF and its receptor type 1 in Lmo3KO and wildtype mice. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: A.M. Savarese, A.W. Lasek Source Type: research
Long-term effects of intermittent alcohol exposure during adolescence on neurobiological substrates of emotion: A role for the endogenous cannabinoid system and neuroinflammation
Intermittent alcohol exposure is a common pattern of adolescent alcohol use that can lead to binge drinking episodes. Alcohol use is known to modulate the endocannabinoid system (ECS), which is involved in neuronal signaling, neuroplasticity, neuroinflammation and emotional behavior. Adolescent male Wistar rats were exposed to 4-week intermittent alcohol intoxication (4 g/kg injections for 4 days/week). Emotionality and cognition were assessed after alcohol deprivation. Subsequently, gene expression of the endocannabinoid signaling and other related mediators was examined in the brain. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Laura Sanchez-Marin, Francisco Javier Pavon, Juan Decara, Juan Suarez, Ana Gavito, Estela Castilla-Ortega, Fernando Rodr íguez de Fonseca, Antonia Serrano Source Type: research
Mathematical modeling of ethanol/stress interactions
While it is well established that stress and alcohol use are mutually related, intricate molecular mechanisms through which ethanol alters the organism ’s response to stress remain only partially understood. To study the complex interactions between ethanol and stress, we have developed a stoichiometric network model to succinctly describe complex birhythmic changes in blood levels of steroid and peptide hormones that constitute the hypothalamic– pituitary–adrenal (HPA) axis and use numerical simulations and approaches from dynamical systems theory to investigate how HPA axis dynamics is affected by acute and chronic...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Željko Čupić, Ana Stanojević, Vladimir M. Marković, Ljiljana Kolar-Anić, Lars Terenius, Vladana Vukojević Source Type: research
Activation of PPAR γ modulates the mesolimbic dopamine transmission and attenuates alcohol drinking in alcohol-preferring rats
The peroxisome proliferator-activated receptor gamma (PPAR γ is one of the three isoforms of the PPARs family, known for its role in adipogenesis and glucose metabolism. An interesting hint come from the discovery of PPARγ in the ventral tegmental area (VTA) dopaminergic neurons (Sarruf et al., 2009) which suggest a potential role of this receptor in the regulation of reward processing and motivated behavior in drug addiction. Furthermore, evidences demonstrated that pioglitazone, a selective agonist of PPARγ suppress alcohol drinking and relapse to alcohol seeking in msP alcohol-preferring rats (Stopponi et al., 2011). (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Yannick Fotio, Roberto Ciccocioppo Source Type: research
Nicotinamide adenine einucleotide reverses hepatic molecular chaperones abnormalities and alleviates experimental alcoholic steatohepatitis in mice
Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase that maintains liver homeostasis and hepatic metabolic function. One of the key intermediate of NAD+ is nicotinamide mononucleotide (NMN). The aim of the present study was to test the ability of NMN to reverse ethanol-mediated aberrant SIRT1 signaling by using wild-type (WT) and liver-specific SIRT1 knockout (Sirt1LKO) mice. Utilizing the Gao-binge ethanol feeding protocol, eight groups of matched WT and Sirt1LKO mice were pair-fed ethanol containing or control diets. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Y. Han, C. Kim, A. Jogasuria, X. Hu, J. Wang, H. Shen, J. Wu, M. You Source Type: research
