Changes in neuronal excitability and synaptic plasticity are increasingly recognized as cellular substrates of the long-term effects of drugs of abuse. The lateral subdivision of the bed nucleus of the stria terminalis (BNST) is involved in stress responses and in the long-lasting motivational dysregulation associated with drug dependence. We observed that high frequency stimulation (HFS) of the area of the stria terminalis in BNST slices in vitro induced a long term potentiation (LTP) of intrinsic excitability and a persistent increase in the temporal precision of firing of neurons in the juxtacapsular subdivision of the lateral BNST (jcBNST). Induction of this form of neuronal plasticity in the jcBNST was impaired during protracted withdrawal in rats with a history of dependent intake of alcohol, cocaine or heroin. In this application we propose to investigate the induction mechanisms of LTP of intrinsic excitability and temporal fidelity of jcBNST neurons in ethanol dependent rats. The impaired plasticity of the jcBNST described here could be relevant to the emotional dysregulation long hypothesized to underlie the transition to compulsive drug taking in dependent individuals. To address this hypothesis, it is proposed to investigate if treatments that have been shown to reduce increased drinking in dependent rats and reinstatement of alcohol-seeking behavior restore LTP of intrinsic excitability and temporal fidelity of jcBNST neurons in ethanol dependent rats. The elucidation of the mechanisms behind the changes in the jcBNST in animals with a history of alcohol dependence is likely to have heuristic value for the understanding of the neurobiological bases of drugs of abuse.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA016587-05
Application #
8239593
Study Section
Neurotoxicology and Alcohol Study Section (NAL)
Program Officer
Liu, Qi-Ying
Project Start
2008-04-15
Project End
2014-03-31
Budget Start
2012-04-01
Budget End
2014-03-31
Support Year
5
Fiscal Year
2012
Total Cost
$324,587
Indirect Cost
$153,301
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Szucs, Attila; Berton, Fulvia; Nowotny, Thomas et al. (2010) Consistency and diversity of spike dynamics in the neurons of bed nucleus of stria terminalis of the rat: a dynamic clamp study. PLoS One 5:e11920
Francesconi, Walter; Berton, Fulvia; Koob, George F et al. (2009) Intrinsic neuronal plasticity in the juxtacapsular nucleus of the bed nuclei of the stria terminalis (jcBNST). Prog Neuropsychopharmacol Biol Psychiatry 33:1347-55
Francesconi, Walter; Berton, Fulvia; Repunte-Canonigo, Vez et al. (2009) Protracted withdrawal from alcohol and drugs of abuse impairs long-term potentiation of intrinsic excitability in the juxtacapsular bed nucleus of the stria terminalis. J Neurosci 29:5389-401