Item Details

title

A Study on the Effects of Chronic Alcohol and Withdrawal on the Glutamate, GABA, and Dopamine Systems in the Basolateral Amygdala of Sprague Dawley Rats

author

Diaz, Marvin

abstract

Alcoholism, a significant issue in society, has been correlated with anxiety disorders. Specifically, severe anxiety experienced during withdrawal from alcohol significantly increases the relapse rate in recovering alcoholics. Therefore, understanding the changes that occur in the brain regions involved in anxiety may help in developing new pharmacological therapies to treat alcohol withdrawal-induced anxiety. The amygdala, in particular the basolateral amygdala (BLA), has been shown to be an important brain region in initiating and processing sensory information pertaining to anxiety-related stimuli in humans and rodents. The BLA also plays a major role in alcohol exposure as different exposures to alcohol can have profound effects on BLA physiology, in particular synaptic transmission. The primary BLA neurotransmitter systems that influence BLA-output consist of the glutamate (excitatory) and GABA (inhibitory) systems. Extensive evidence suggests that these two systems are significantly altered by chronic alcohol and withdrawal, resulting in ‘hyperexcitable’ BLA-output and anxiety-like behavior. Furthermore, the BLA inhibitory GABA system is modulated by the midbrain via the dopamine system, suggesting another potential target for the effects of chronic alcohol and withdrawal on anxiety-like behavior. Therefore, the main goal of this study was to examine the effects of chronic ethanol exposure and withdrawal on the BLA glutamate and GABA systems, and to characterize how the dopamine (DA) system modulates BLA GABAergic transmission. In chapter II we investigated the effects of chronic intermittent ethanol (CIE) and withdrawal (WD) on glutamatergic synaptic transmission in the BLA. This set of studies suggests that glutamatergic function is increased at BLA synapses in CIE and WD treated animals, albeit via distinct mechanisms. Furthermore, we found that manipulations of the glutamate system altered anxiety-like behaviors. In chapter III we examined the effects of CIE and WD on two populations of GABAergic inhibitory interneurons in the BLA. We found that CIE and WD differentially affect GABAergic transmission from local feed-back interneurons and feed-forward lateral paracapsular cells (LPCs), resulting in an overall suppression of GABAergic inhibition during withdrawal. In addition, the effects of acute ethanol on the two interneuron populations are not altered by CIE or WD. In chapter IV we characterized DA modulation of alcohol-naïve BLA GABAergic transmission at local and LPC synapses. This study revealed that inhibition of DA D3 receptors (D3Rs) in the BLA of alcohol-naïve adolescent Sprague Dawley rats can significantly alter anxiety-like behavior. Moreover, these results led us to uncover a functional role of D3Rs at local and LPC synapses as well as a concentration dependent effect of DA at local synapses. Finally, in chapter V we focused on determining the effects of CIE and WD on the DA modulation of GABAergic transmission. Preliminary data suggest that there are age-dependent changes in DA modulation of BLA GABAergic transmission. Additionally, CIE and WD appear to differentially alter DA modulation of GABAergic transmission from local and LPC synapses in older animals. Taken together, these studies suggest that chronic ethanol exposure and withdrawal shift the balance between glutamate and GABA, potentially through alterations in the dopamine system, resulting in an increase in withdrawal-induced anxiety-like behavior.

subject

Neurophysiology

Pharmacology

contributor

Godwin, Dwayne (committee chair)

McCool, Brian (committee member)

Nader, Michael (committee member)

Weiner, Jeffrey (committee member)

Jones, Sara (committee member)

date

2009-05-13T18:04:41Z (accessioned)

2010-06-18T18:58:07Z (accessioned)

2009-05-13T18:04:41Z (available)

2010-06-18T18:58:07Z (available)

2009-05-13T18:04:41Z (issued)

degree

Neuroscience (discipline)

identifier

http://hdl.handle.net/10339/14735 (uri)

language

en_US (iso)

publisher

Wake Forest University

rights

Release the entire work for access only to the Wake Forest University system for one year from the date below. After one year, release the entire work for access worldwide. (accessRights)

type

Dissertation