Top-down modulation of interoception – a new frontier for drug and alcohol addiction treatments? - Dr. Martin Paulus
May. 14th 2012 - 3:45pm - CMHC, Room W-2Interoception, the sense of the physiological state of the body, is an important process that underlies the connection between external stimuli and the internal state of the individual. The insula cortex and associated brain structures are important brain substrates that mediate interoceptive processes. We have previously proposed that dysfunction in this neural circuitry contributes significantly to the pathology that makes individuals susceptible to drug and alcohol use disorders. We will present several data sets that provide converging evidence that the neural systems of the insula and associated structures play an important role in both alcohol and drug related states. However, to go beyond the examination of the underlying neural circuitry, we are proposing that modulating these systems may be a pathway to build “resilience” against the susceptibility to drug and alcohol related problems. Although this research is at a very early stage, it provides an entirely new pathway to modify behaviors that put individuals at risk for addiction.
Impact of chronic alcohol on the neural circuits regulating extinction and decision-making - Dr. Andrew Holmes
April. 2nd 2012 - 3:45pm - CMHC, Room W-2
As with other addictions, alcoholism can be usefully conceptualized as a progressive disease involving impairments in executive and cognitive processes that are critically dependent upon functions of the prefrontal cortex and its interactions with subcortical structures such as the amygdala and striatum. An emerging body of evidence, from studies in rodents, will be discussed that demonstrate profound effects of chronic alcohol exposure on the structure and certain in vivo functions of the prefrontal cortex, amygdala and dorsal striatum. The focus will be on alcohol’s effects on fear extinction, as an exemplar of a fronto-amygdala function with direct translational relevance to appreciating how alcohol might serve as a risk factor for extinction-impaired neuropsychiatric conditions, such as PTSD.
Ethanol Dependence and relapse Drinking: Role of Adaptations in Glutamate Transmission and Treatment Implications - Dr. Howard Becker
March. 19th 2012 - 3:45pm - CMHC, Room W-2Alcohol dependence results in a number of neuroadaptations in brain that play an important role in driving excessive levels of drinking and increased relapse vulnerability. Dr. Becker will describe studies that demonstrate that alterations in glutamate tone in the nucleus accumbens (NAc), a critical brain region within reward circuitry, influence regulation of alcohol consumption and mediate escalated drinking associated with dependence. Using a mouse model of ethanol dependence and relapse drinking, we have shown that repeated cycles of chronic intermittent ethanol (CIE) exposure produces robust escalation of voluntary ethanol drinking that results in significant elevation in blood and brain ethanol levels. Using in vivo microdialysis procedures, increased extracellular glutamate levels in the NAc were shown following CIE exposure, an effect that lasted well beyond acute withdrawal. These data suggest that elevated glutamate activity in the NAc may drive the increased drinking noted in the CIE model. Pharmacological studies that directly manipulate glutamate tone in the NAc provide general support for this hypothesis: increasing glutamate tone via bilateral intra-NAc injection of a non-selective glutamate reuptake blocker (DL-threo-beta-Benzyloxyaspartic acid; TBOA) significantly increased drinking in nondependent mice to dependent levels, while decreasing glutamatergic activity via bilateral injection of a mGluR2/3 agonist (LY379268) significantly reduced drinking in dependent mice to nondependent levels of intake. Collectively, these data suggest that ethanol dependence produces enduring changes in glutamate activity in the NAc and that increased glutamate tone in the NAc may promote/drive, at least in part, excessive ethanol drinking associated with dependence. Studies aimed at elucidating mechanisms underlying this effect along with treatment implications for these findings will be discussed.
Alcohol Dependence: Identifying Genetic and Epigenetic Factors Associated with Intermediate Neurobiological Phenotypes - Dr. Kent Hutchison
Feb. 13th 2012 - 3:45pm - CMHC, Room W-2
The etiology of alcohol dependence is related to changes in the neuronal systems involved in the anticipation of reward and executive control. Genetic and epigenetic variations that are associated with individual differences in these systems may be important in terms of predicting the course of the disorder and the effectiveness of treatment approaches. To identify these genetic and epigenetic variations, intermediate neurobiological phenotypes are used as a bridge to link genetic variation with clinical variables. The intermediate phenotypes include measures of BOLD response to alcohol cues as well as measures of functional connectivity. In a recent study, an exploratory genome wide analysis identified a set of single nucleotide polymorphisms (SNPs) that were associated with large clusters of brain activation as well as focal activation of the dorsal striatum after exposure to alcohol cues. On the epigenetic front, recent analyses have identified an epigenetic site near the DRD2 gene that is related to BOLD response to alcohol cues, impaired control over alcohol consumption, and clinical outcomes. In sum, preliminary data suggest that genetic and epigenetic biomarkers may be related to functional brain changes in response to alcohol cues as well as clinical measures.