The Cellular Electrophysiology Project (Director: Marisa Roberto, Co-Director: George Siggins) proposes to continue cellular studies of the role of neurotransmission in alcohol drinking and dependence and is based on behavioral findings that the basolateral (BLA) and central (CeA) amygdala nuclei are key brain areas involved in stress reactions and alcohol dependence. This renewal application will focus on the overall hypotheses that the transition from low levels of drinking to chronic binge drinking is driven by decreased activity in endocannabinoid systems in ?reward circuits? in the amygdala and that the transition from binge drinking to dependence is also driven by recruitment of a dysregulated stress system driven by corticotropinreleasing factor (CRF) and the neuronal pentraxin Narp. We will use amygdala slice preparations to functionally and morphologically characterize CeA and BLA neurons (Specific Aims 1 and 2) and neurocircuitry (Specific Aims 1-3) involved in responses to ethanol, cannabinoids, and CRF and in the progression from binge drinking to dependence.
Specific Aim 1 is designed to test the hypothesis that binge drinking and/or dependence will differentially alter responses to cannabinoids (CB1 receptor agonists and antagonists) in specific neurons and synapses in the BLA and CeA.
Specific Aim 2 will test the hypothesis that withdrawal from alcohol bingeing or dependence will alter synaptic glutamatergic transmission both within and between the BLA and CeA and/or their responses to CRF and acute ethanol via changes in Narp levels.
Specific Aim 3 is designed to use neuronal filling with biocytin and tracing via retrograde labeling from brain-region targets of BLA and CeA neurons, such as the bed nucleus of stria terminalis, to test the hypothesis that alterations in synaptic properties within specific neurons and neurocircuitries are involved in binge drinking, dependence, and withdrawal and may be associated with changes in the endocannabinoid and CRF or Narp systems. This project will use BLA and CeA brain slices and standard intracellular and whole-cell clamp methods and a battery of measures to assess the pre- vs. postsynaptic sites of action of ethanol and ligand effects and will involve collaborations with the Parsons, Zorrilla, and Mandyam components and Viral Vector and Animal Models/Biological Measurement Cores. The project should provide important new information on the possible sequelae of ethanol binge drinking to dependence at the cellular, microcircuitry, synaptic, and ion channel levels.
This project will examine the cellular and synaptic mechanisms in the amygdala likely to underlie binge alcohol drinking and alcohol dependence. Because such mechanisms are also integrated within several other TSRI Alcohol Research Center projects and involve potentially ?druggable? sites, the present studies represent new directions in attempts to validate drug targets for the prevention or treatment of binge drinking and dependence on alcohol
|Kim, Airee; Zamora-Martinez, Eva R; Edwards, Scott et al. (2015) Structural reorganization of pyramidal neurons in the medial prefrontal cortex of alcohol dependent rats is associated with altered glial plasticity. Brain Struct Funct 220:1705-20|
|Cohen, Ami; Soleiman, Matthew T; Talia, Reneta et al. (2015) Extended access nicotine self-administration with periodic deprivation increases immature neurons in the hippocampus. Psychopharmacology (Berl) 232:453-63|
|Montane Jaime, Lazara Karelia; Shafe, Samuel; Liang, Tiebing et al. (2014) Subjective response to alcohol and ADH polymorphisms in a select sample of young adult male East Indians and Africans in Trinidad and Tobago. J Stud Alcohol Drugs 75:827-38|
|Buck, Cara L; Malavar, Jordan C; George, Olivier et al. (2014) Anticipatory 50 kHz ultrasonic vocalizations are associated with escalated alcohol intake in dependent rats. Behav Brain Res 271:171-6|
|Herman, Melissa Ann; Roberto, Marisa (2014) Cell-type-specific tonic GABA signaling in the rat central amygdala is selectively altered by acute and chronic ethanol. Addict Biol :|
|Kallupi, Marsida; Oleata, Christopher S; Luu, George et al. (2014) MT-7716, a novel selective nonpeptidergic NOP receptor agonist, effectively blocks ethanol-induced increase in GABAergic transmission in the rat central amygdala. Front Integr Neurosci 8:18|
|Rivier, Catherine (2014) Role of hypothalamic corticotropin-releasing factor in mediating alcohol-induced activation of the rat hypothalamic-pituitary-adrenal axis. Front Neuroendocrinol 35:221-33|
|Buck, Cara L; Vendruscolo, Leandro F; Koob, George F et al. (2014) Dopamine D1 and *-opioid receptor antagonism blocks anticipatory 50ýýkHz ultrasonic vocalizations induced by palatable food cues in Wistar rats. Psychopharmacology (Berl) 231:929-37|
|Gilpin, Nicholas W; Roberto, Marisa; Koob, George F et al. (2014) Kappa opioid receptor activation decreases inhibitory transmission and antagonizes alcohol effects in rat central amygdala. Neuropharmacology 77:294-302|
|Zorrilla, Eric P; Logrip, Marian L; Koob, George F (2014) Corticotropin releasing factor: a key role in the neurobiology of addiction. Front Neuroendocrinol 35:234-44|
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