Myelinated axons increase in the anterior cingulate cortex early in adolescence and are negatively impacted by alcohol
Drinking at a young age —especially heavy episodic binge drinking—is associated with reduced myelinated fiber tracks in the frontal lobes, emotional dysregulation, and an increased risk of alcohol use disorder in adulthood. Our lab has begun delineating these neural and behavioral relationships to examine the hypothesi s that alcohol interrupts myelination of stress circuits to negatively affect mental health trajectories and addiction vulnerability later in life. We have focused on the anterior cingulate cortex—a subregion of the prefrontal cortex that contains axons from the basolateral amygdala and is involve d in...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: W.M. Vargas, A. Silva-Gotay, E. Tavares, H.N. Richardson Source Type: research
Sex differences in alcohol seeking behaviors and their modulation by acute and chronic stress
The incidence of alcohol use disorders (AUDs) in women is steadily increasing. Moreover, data suggest that women progress more quickly than men from social use to dependence. Therefore, women are increasingly viewed as a vulnerable population for the development of AUDs, yet the role of sex and sex hormones on motivation for and relapse to alcohol seeking has been little studied. In addition, dysregulation of the HPA axis is associated with the development of AUDs; however, despite substantial evidence for sex differences in the stress response, the effects of stress on alcohol-motivated behaviors in females has not been e...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Megan Bertholomey, Vidhya Nagarajan, Mary M. Torregrossa Source Type: research
Differential susceptibility of male and female amygdala to corticosterone and alcohol
Alcohol use disorders are pervasive, chronically relapsing conditions, and stress is a primary trigger of relapse. Females develop stress-related disorders more frequently than males and may thus be uniquely sensitive to stress-induced alcohol consumption. The neural underpinnings of sexually dimorphic stress sensitivity and its impact on alcohol use are currently incompletely understood. We hypothesized that stress or the stress-induced hormone corticosterone would generate greater changes in females than males, which could promote heightened alcohol relapse-like behavior. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Marian L. Logrip, Sean C. Gainey, Christopher Oleata, Marisa Roberto Source Type: research
Sex differences and the role of sex hormones in stress reactivity, emotion regulation and craving in drug and alcohol dependence
Aims: Sex hormones are known to modulate the subjective effects of drugs. In three studies, we examined the effects of progesterone and its neuroactive derivative allopregnanolone (ALLO) on emotional and cognitive regulation, stress response, and craving in cocaine and alcohol dependent (CAD) patients. Methods: STUDY 1: The Mayer, Salovey, and Caruso Emotional Intelligence Test (MSCEIT) was administered to 98 CAD (55 M/43 F) and 56 healthy (28 M/28 F) individuals. Performance was also assessed by menstrual cycle in the women. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: V. Milivojevic, H.C. Fox, R. Sinha Source Type: research
Recent results on ghrelin in alcohol use disorders
Recent preclinical and clinical studies suggested ghrelin to have an orexigenic role in the regulation of appetite and energy balance. Thereby, food consumption in humans is not only a response to an intrinsic sensation of hunger which ensures energy homeostasis but also a result of neuronal processes influenced by the rewarding and positively reinforcing features of food. Preclinical studies also provided support for an important role of ghrelin in the neurobiology of addiction-related reward pathways, affecting the self-administration of alcohol and drugs as well as conditioned place preference. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Falk Kiefer, Anne Koopmann Source Type: research
Ghrelin as potential new pathway toward medication development for alcohol use disorder: Recent clinical data
The rewarding properties of natural and chemical reinforcers are mediated via multiple and complex pathways in the brain. There is an underlying disruption in reward processing in animal models of and individuals with addictions. This raises the possibility that endocrine signals from the gut traditionally known to regulate food intake may play an important role in reward regulation as well as in development of drug dependence. Dr. Leggio will present recent clinical data suggesting that GLP-1 and ghrelin represent potential new pathways toward medication development for alcohol use disorder. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Lorenzo Leggio Source Type: research
Oxytocin blocks compulsive-like alcohol drinking in rats
We hypothesized that brain signaling by the neuropeptide oxytocin, known to be involved in both stress and reward function, contributes to compulsive alcohol drinking. To test our hypothesis, we used a preclinical model of alcohol dependence that reliably produces somatic and motivational signs of dependence. Wistar rats were trained to lever press for access to alcohol and then either made alcohol dependent (via repeated cycles of alcohol vapor exposure and withdrawal) or exposed to air to provide a nondependent control group. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Brendan Tunstall Source Type: research
Oxytocin reduces alcohol self-administration and stress-induced alcohol relapse behavior in mice
Recent evidence implicates the neuropeptide oxytocin (OXT) as a potential therapeutic for alcoholism. The present studies examined the effects of systemic administration of OXT on alcohol self-administration and stress-induced relapse-like behavior. Adult male C57BL/6J mice were trained using standard operant procedures to lever respond on a fixed ratio (FR4) schedule for 12% (v/v) alcohol or 5% (w/v) sucrose reinforcement (20 ul) during daily 20-min sessions. In a second study, after establishing stable alcohol self-administration and then extinction testing, reinstatement of alcohol responding was provoked by yohimbine (...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Howard C. Becker, Courtney E. King, William C. Griffin Source Type: research
Dopamine signaling in the nucleus accumbens can bidirectionally regulate ethanol seeking behavior
During the last several decades, a large body of evidence has demonstrated an important role for mesolimbic dopamine (DA) signaling in the etiology of alcohol use disorder. Surprisingly, despite much effort, it is still unclear how DA controls the initiation and suppression alcohol drinking. This knowledge is crucial for the development of effective pharmacotherapies aimed at treating alcohol addiction. Here, we used optogenetics to explore the causal link between phasic and tonic patterns of DA transmission in the nucleus accumbens (NAcc) and ethanol seeking behavior. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Evgeny A. Budygin, Jeff L. Weiner Source Type: research
Studying behavioural control in rodents and humans
A major problem in using animal studies to understand human disorders such as alcohol abuse is the mismatch between what is actually studied in animals and humans. While many tests appear to have “face validity”, such face validity is often only in the eye of the beholder. An approach to overcoming the mismatch between animal and human research is to develop methods that are homologous across species. We have developed several methods for evaluating cognitive abilities in humans based on rodent tests of cognitive performance (e.g. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Dai Stephens Source Type: research
Neurocognitive endophenotypes for hazardous alcohol use
During late adolescence and early adulthood frontal to subcortical neural connectivity continues to mature. Data from animal models suggest that during this developmental window, these circuits are acutely sensitive to alcohol insult, resulting in neurocognitive deficits that persist into adulthood. Despite this knowledge, relatively little is yet know about the neurocognitive abnormalities associated with hazardous alcohol use in adolescence. To address this issue, we evaluated resting state functional connectivity of mesocortical circuitry in a sample of healthy adults (ages 18-40) that did not meet DSM criteria for an a...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: T.H. McKim, G. Guo, S. Lane, M.H. Parrish, C.T. Smith, S.H. Oppler, M. Menceloglu, K. Gates, D.L. Robinson, C.A. Boettiger Source Type: research
Examining phenotype by treatment interactions in alcohol use disorder clinical trials
Alcohol use disorder (AUD) is a heterogeneous disorder characterized by a variety of developmental etiologies and diverse symptom profiles. Over the past 50+ years many have attempted to characterize types of alcohol drinkers based on behavioral, developmental, and personality aspects. More recent work in the field has focused on genetic and neurobiological markers of risk and AUD treatment response. From this work, there is broad recognition that relief of stress and negative affect (negative reinforcement mechanism) is a primary predictor of relapse among AUD populations. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Katie Witkiewitz, Corey Roos, Karl Mann, Megan Kirouac, Tessa Frohe, Stephen Maisto, Kevin Vowles Source Type: research
Systemic and site-specific inactivation of the kappa opioid receptor system reduces binge-like drinking and stress-enhanced ethanol consumption in dependent C57BL/6J mice
Stressful experiences can exacerbate alcohol use disorders by promoting the transition from casual alcohol (ethanol) consumption to dependence and by triggering relapse in abstinent alcoholics. Our laboratory has developed a preclinical model of stress-enhanced drinking in ethanol dependent mice. Specifically, daily forced swim stress 4 hr prior to voluntary access to 15% ethanol results in an elevation of ethanol consumption in mice exposed to chronic intermittent ethanol (CIE) vapor, but not in non-dependent control mice. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: R.I. Anderson, H.L. Haun, W.C. Griffin, H.C. Becker Source Type: research
Regulation of dopamine and dynorphin/KOR function by chronic ethanol and withdrawal in mice and monkeys
Alcoholism is a widespread disorder that is particularly pernicious, given the exceedingly high rates of relapse. It is believed that cycles of chronic relapse are driven largely by states of negative affect (such as depression and anxiety) during withdrawal, which may be caused in part by increased kappa-opioid receptor (KOR) signaling and hypodopaminergia. We have documented numerous contributors to hypodopaminergia in the nucleus accumbens following ethanol withdrawal in both rodents and non-human primates. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: K.M. Holleran, A. Karkhanis, J.H. Rose, C.A. Siciliano, K.A. Grant, S.R. Jones Source Type: research
Alcohol drinking induced alterations in dynorphin signaling in the extended amygdala
The extended amygdala, principally comprised of the Central Amygdala (CeA) and the Bed Nucleus of the Stria Terminalis (BNST), has been shown to be important for the negative reinforcing aspects of drugs of abuse. Behavioral pharmacology studies have shown that systemic administration of KOR antagonists (Walker& Koob 2008) and site-specific administration into the CeA (Kissler et al. 2014) decrease alcohol self-administration in dependent animals. In this symposium, Anderson et al. will show that CeA dynorphin neurons regulate binge consumption of alcohol in the Drinking in the Dark (DID) paradigm. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Daniel Bloodgood Source Type: research
