The shell nucleus accumbens (Nacc) comprises a critical component of the extended amygdala that receives a dopaminergic (DA) projection from the ventral tegmental area a glutamatergic (GLU) projection from the basolateral amygdala. Historically, the GABAergic projection neurons of the Nacc have been the focus of efforts to understand the alterations in neurochemical and synaptic structure and function that may underlie drug dependence and reinforcement phenomena. However, it is becoming increasingly apparent the cholinergic interneurons of the nucleus accumbens (CHI-NAccs) have experienced a relative dearth of analysis in drug abuse. This lack of analysis of these cells is especially disconcerting since it is apparent that these neurons are (1) critical neuronal integrators and modulators (2) possess key receptors and receptor-activated intracellular pathways important for plasticity and drug abuse, (3) express LTP and learning (4) exert powerful influences onto output projection neurons and (5) are compromised in clinical disorders such as schizophrenia, which can be induced by drug abuse. This accumulating evidence has led the P1 to hypothesize that these CHI-NAss may play a critical role in excessive ethanol consumption since these neurons share similar cellular, molecular and behavioral mechanisms with those involved in addiction for preliminary data examining the expression of immediate early genes (IEGs) in cholinergic interneurons following the self-administration of cocaine in rats). This project will test the hypothesis that ethanol induced neuroadaptation (i.e. changes in IEGs and receptors) and synaptic rewiring occurs on CHI-NAccs via """"""""Hebbian- like"""""""" associative convergence of the activity of VTA and amygdaloid afferents. The following 4 specific aims are designed as a comprehensive test of this hypothesis. We seek to characterized ethanol induced IEG expression, dynamic trafficking of key DA/GLU synaptic components and synaptic rewiring within shell nucleus accumbens cholinergic neuronal networks in animal models of excessive ethanol consumption. We will also seek to determine the alterations of key DA/GLU components in relation to ethanol mice genetic models and ethanol exposure. The findings from this work should contribute to a better understanding of the neuronal mechanisms that cause or predict excessive ethanol consumption and toward the development of improved behavioral and pharmacological prevention treatments for alcoholism and alcohol abuse.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project--Cooperative Agreements (U01)
Project #
1U01AA013497-01
Application #
6449676
Study Section
Special Emphasis Panel (ZAA1-DD (20))
Program Officer
Noronha, Antonio
Project Start
2001-09-27
Project End
2006-08-31
Budget Start
2001-09-27
Budget End
2002-08-31
Support Year
1
Fiscal Year
2001
Total Cost
$170,949
Indirect Cost
Name
University of Texas Austin
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
City
Austin
State
TX
Country
United States
Zip Code
78712
Bao, Hong; Berlanga, Monica L; Xue, Mingshan et al. (2007) The atypical cadherin flamingo regulates synaptogenesis and helps prevent axonal and synaptic degeneration in Drosophila. Mol Cell Neurosci 34:662-78
Hendricson, Adam W; Maldve, Regina E; Salinas, Armando G et al. (2007) Aberrant synaptic activation of N-methyl-D-aspartate receptors underlies ethanol withdrawal hyperexcitability. J Pharmacol Exp Ther 321:60-72
Maiya, R; Ponomarev, I; Linse, K D et al. (2007) Defining the dopamine transporter proteome by convergent biochemical and in silico analyses. Genes Brain Behav 6:97-106
Camp, Marguerite Charlotte; Mayfield, Roy Dayne; McCracken, Mandy et al. (2006) Neuroadaptations of Cdk5 in cholinergic interneurons of the nucleus accumbens and prefrontal cortex of inbred alcohol-preferring rats following voluntary alcohol drinking. Alcohol Clin Exp Res 30:1322-35
Berlanga, Monica Lisa; Simpson, Taylor Kathryn; Alcantara, Adriana Angelica (2005) Dopamine D5 receptor localization on cholinergic neurons of the rat forebrain and diencephalon: a potential neuroanatomical substrate involved in mediating dopaminergic influences on acetylcholine release. J Comp Neurol 492:34-49
Maldve, Regina E; Chen, Xiaochun; Zhang, Tao A et al. (2004) Ethanol selectively inhibits enhanced vesicular release at excitatory synapses: real-time visualization in intact hippocampal slices. Alcohol Clin Exp Res 28:143-52
Diaz, Laurea M; Maiya, Rajani; Sullivan, Matthew A et al. (2004) Sindbis viral-mediated expression of eGFP-dopamine D1 receptors in situ with real-time two-photon microscopic detection. J Neurosci Methods 139:25-31
Herring, Bruce E; Mayfield, R Dayne; Camp, Marguerite C et al. (2004) Ethanol-induced Fos immunoreactivity in the extended amygdala and hypothalamus of the rat brain: focus on cholinergic interneurons of the nucleus accumbens. Alcohol Clin Exp Res 28:588-97
Hendricson, Adam W; Thomas, Mark P; Lippmann, Melanie J et al. (2003) Suppression of L-type voltage-gated calcium channel-dependent synaptic plasticity by ethanol: analysis of miniature synaptic currents and dendritic calcium transients. J Pharmacol Exp Ther 307:550-8
Alcantara, Adriana A; Chen, Violeta; Herring, Bruce E et al. (2003) Localization of dopamine D2 receptors on cholinergic interneurons of the dorsal striatum and nucleus accumbens of the rat. Brain Res 986:22-9