Adaptations in basal and hypothalamic-pituitary-adrenal-mediated deoxycorticosterone responses following ethanol self-administration in cynomolgus monkeys
Acute ethanol activates the hypothalamic-pituitary-adrenal (HPA) axis, while long-term exposure results in a dampened neuroendocrine state, particularly with regards to the primary endpoint, cortisol. However, it is unknown if this dampened neuroendocrine status also influences other adrenocortical steroids. Plasma levels of the mineralocorticoid and neuroactive steroid precursor deoxycorticosterone (DOC) are altered by pharmacological challenges of the HPA axis in cynomolgus monkeys. The present study is an extensive investigation of the mechanisms related to HPA axis activation that regulate DOC concentration over the co...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Vanessa A. Jimenez, Patrizia Porcu, A. Leslie Morrow, Kathleen A. Grant Source Type: research
Effects of oxytocin on stress-induced reinstatement of alcohol-seeking in mice with and without a history of stress
Recently, the central oxytocin (OXT) system has emerged as a potential therapeutic target for alcohol use disorders. Here, we examined the effects of OXT treatment on stress-induced reinstatement of ethanol-seeking behavior and the ability of prior stress to sensitize this response, using a model of chronic stress induced by the predator odor, trimethylthiazoline (TMT). Adult C57BL6/J mice were trained to orally self-administer ethanol (12% v/v) under a fixed ratio operant schedule. After stable baseline ethanol responding and intake was established, mice were exposed to 1% TMT in saline for 15 mins for five consecutive da...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: C.E. King, J.F. McGinty, H.C. Becker Source Type: research
Neuroadaptations in cingulate cortex glucocorticoid signaling in alcohol dependence
Alcohol Use Disorder (AUD) is a chronic, relapsing psychiatric disorder that is characterized by the development of motivational symptoms (e.g., escalation of alcohol intake) and the parallel emergence of negative emotional states (e.g., dysphoria, anxiety, pain). Consequently, the transition from recreational, limited alcohol consumption to uncontrolled, escalated intake is proposed to involve a transition from positive to negative reinforcement mechanisms. Our rodent model of alcohol dependence, which utilizes chronic intermittent ethanol vapor (CIEV) exposure, produces a constellation of motivational symptoms of depende...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: M. Adrienne McGinn, Amanda R. Pahng, Kimberly N. Edwards, Scott Edwards Source Type: research
Effects of chronic ethanol exposure and withdrawal on glutamatergic signaling at two afferent projections into the rat lateral/basolateral amygdala
Increased anxiety during alcohol withdrawal (WD) is a central characteristic of alcohol dependence and has been reported as a common, underlying cause of relapse. The lateral/basolateral amygdala (BLA) has been identified as a critical component of the neural circuitry that regulates a variety of emotional behaviors, including anxiety. Our laboratory has recently shown that chronic ethanol exposure and WD produce distinct synaptic alterations in the BLA that are input- and timing-specific. However, little is known about how specific inputs from distinct upstream brain regions are affected by chronic ethanol exposure. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Molly M. McGinnis, Melissa M. Morales, Nancy J. Alexander, Brian A. McCool Source Type: research
Gonadal hormones contribute to alcohol consumption in response to exercise restriction
Stress is a response to environmental perturbation that results in a wide range of physiological and behavioral changes, which can include increased alcohol (EtOH) consumption. Biological sex is one factor that has been associated with differential stress sensitivity and risk for excessive drinking, possibly dependent on gonadal hormones. Our goal is to understand the potential contributions of estrogen and testosterone to voluntary EtOH consumption during stress. We measure free choice self-administration by C57BL/6J mice in a modified drinking in the dark paradigm, which for some animals includes stress introduced by man...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Colleen E. McGonigle, Todd B. Nentwig, Grace Leung, Zach Kozick, Dasha Kostyuchek, Judy Grisel Source Type: research
Altered sensitivity to the anxiolytic and rewarding properties of alcohol in mice which carry the BDNF valine 68 to methionine polymorphism
The brain derived neurotrophic factor (BDNF) plays a major role in structural and functional neuronal plasticity. We previously showed that corticostriatal BDNF gates alcohol intake. The valine (Val) 66 to methionine (Met) substitution is a common genetic variant in the human BDNF gene which is associated with multiple psychiatric disorders, as well as altered anxiety phenotypes and alcohol use. Using a transgenic mouse homologue of the human allele (Val68/Met68) we recently reported that carrying the Met68BDNF polymorphism increases the risk of developing excessive and compulsive alcohol drinking despite of negative conse...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Samuel A. Sakhai, Nadege Morisot, Dorit Ron Source Type: research
Predator odor stress activates corticotropin-releasing factor (CRF) neurons in rat brain
Post-traumatic stress disorder and alcohol use disorder are highly co-morbid. One possible mediator of this co-morbidity is corticotropin-releasing factor (CRF). CRF is highly expressed in the central amygdala (CeA), and stress and alcohol each dysregulate brain CRF signaling, as well as CeA activity. Re-exposure to stress-paired stimuli increases neuronal activation, as measured by ERK phosphorylation, in CeA of rats that display high avoidance of a predator odor-paired chamber (Avoiders). The purpose of Experiment 1 was to determine the effect of predator odor stress on CRF neuron activation in limbic brain regions. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: A.L. Schreiber, A.M. Whitaker, N.W. Gilpin Source Type: research
Orexin/hypocretin receptor 2 (HCRTR2) in alcohol dependence diagnosis and severity: Role of HCRTR2 rs2653349 polymorphism
Preclinical studies have implicated the hypocretin/orexin system, and specifically the orexin/hypocretin receptor 1 (HCRTR1), in both alcohol and drug-seeking behaviors and stress. Recently, the role of HCRTR 2 in mediating addictive behaviors has emerged. Selective HCRTR2 antagonism has been shown to reduce both ethanol and heroin self-administration. In humans, the nonsynonymous HCRTR2 rs2653349 (1246G>A) polymorphism has been associated with increased risk for nicotine and methamphetamine use, and with panic disorders. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Primavera A. Spagnolo, Timothy Klepp, Melanie Schwandt, David Goldman Source Type: research
Ketamine inoculation immediately after forced ethanol abstinence blocks the development of time-dependent affective disturbances
Withdrawal from chronic alcohol administration produces affective disturbances that may promote alcohol use disorders. Recent studies have shown that female C57BL/6J mice undergoing contingent two-bottle choice ethanol administration for six-weeks develop significant affective disturbances in depressive-like but not anxiety-like behavior after two-weeks of forced abstinence that is acutely reversed by the antidepressant ketamine. Here we show 1) that the protection via ketamine is sensitive to the CB1 antagonist rimonabant, and 2) that anxiety-like behaviors are present within the early phase of forced abstinence. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Oliver Vranjkovic, Sachin Patel, Danny Winder Source Type: research
The Nociceptin/Orphanin FQ receptor agonist SR-8993 as a candidate therapeutic for alcohol use disorders: Validation in rat models
Introduction: Alcoholism is a complex disorder in which diverse pathophysiological processes contribute to the initiation and progression, resulting in a high degree of heterogeneity among patients. Few pharmacotherapies are presently available, and patient responses to these are variable. The Nociceptin/Orphanin FQ (NOP) receptor has been suggested to play a role both in alcohol reward and in negatively reinforced alcohol seeking. Previous studies have shown that NOP receptor activation reduces alcohol intake in genetically selected alcohol preferring as well as alcohol dependent rats. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Abdul Maruf Asif Aziz, Shaun Brothers, Gregory Sartor, Markus Heilig, Claes Wahlestedt, Annika Thorsell Source Type: research
A novel NOP receptor antagonist decreases alcohol behavior in Marchigian Sardinian alcohol-preferring (msP) rats
Ethanol is one of the most abused substance worldwide. The reinforcing and rewarding property of ethanol are mediated by several neurochemical systems and many different sites in the brain. The N/OFQ and its receptor (NOP) are found throughout the brain, spinal cord and dorsal root ganglia, supporting a role of the N/OFQ-NOP system in the modulation of central functions, including learning and memory, reward, mood, feeding, stress and sensory nociceptive processing. Since its deorphanization, there has been a clear dichotomy in the literature regarding whether an agonist or antagonist would provide therapeutic benefit. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: A.M. Borruto, S. Stopponi, M. Mondaini, M. Ubaldi, R. Ciccocioppo Source Type: research
Reward sensitivity as a mechanism linking social stress with binge drinking in justice-involved adolescents
Relative to children and adults, adolescents show heightened sensitivity to social stress, with peer influence on risk behaviors peaking during this developmental period. Peer risky behavior is a strong predictor of substance use initiation in particular, including alcohol. However, it is unclear what mechanisms guide this relationship. One possibility is that heightened reward sensitivity renders adolescents more susceptible to peer influence, such that risky peer behaviors may facilitate their own risky behaviors (i.e., binge drinking). (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: J.D. Caouette, A.D. Bryan, K.A. Hudson, S.W. Feldstein Ewing Source Type: research
Influence of habitual negative affect on processing of negative facial stimuli in alcoholic patients
Introduction: Neuropsychological studies reported decoding deficits of emotional facial expressions in alcohol-dependent patients (ADP). Habitual negative affect (hNA) could be one of the basic moderators associated with perception biases. Previous neuroimaging studies found altered neural activation patterns in prefrontal and limbic brain areas during emotional facial processing in ADP, predicting also prospective relapse risk. However, studies on hNA influence on neural activation during emotion processing in ADP are lacking so far. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Katrin Charlet, Linda Wulkau, Anne Beck, Anne Jorde, Evangelos Zois, Sabine Vollst ädt-Klein, Martina Kirsch, Henrik Walter, Falk Kiefer, Andreas Heinz Source Type: research
Adolescent social isolation increases excitatory synaptic activity and impairs long term depression in the rat nucleus accumbens core
Our lab has established a rodent model of adolescent social isolation (aSI) which engenders robust and enduring increases in behaviors linked to alcohol addiction vulnerability, including increases in anxiety-like behaviors, ethanol intake and preference. We have recently shown that the basolateral amygdala (BLA), a brain region heavily implicated in the pathophysiology of anxiety and addiction, is hyper-excitable following aSI. The BLA sends glutamatergic projections to other addiction-related brain regions including the ventral hippocampus (vHC) and nucleus accumbens (NAc). (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Sarah E. Ewin, Antoine G. Almonte, Eugenia S. Carter, Jeffrey L. Weiner Source Type: research
Non-substance related addictive disorders: Stress reactivity and relationship to problematic alcohol consumption
Neurobiological similarities between substance use disorders and non-substance related addictive disorders are starting to emerge in the literature. For instance, similar to those with substance use disorder, non-substance related addictive disordered individuals demonstrate both cue-induced craving and response inhibition. Few studies have examined stress system function in individuals with non-substance related addictive disorder, however (although see Geisel et al., 2015). Given that individuals with substance related addictive disorders show dysregulated stress system function function during intoxication, withdrawal, ...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Rebecca Gilbertson, Dustyn Leff Source Type: research
