The proposed project will prepare the applicant for a career as an independent research scientist investigating the neurochemical mechanisms that underlie the motivational and reinforcing aspects of alcohol-directed behaviors. Alcohol-directed behaviors can be conceptually divided into two phases: 1) appetitive or alcohol seeking and 2) consumption or alcohol drinking. It is hypothesized that activation of the GAB A receptor system exerts ethanol-directed behavior, The overall goal of this proposal is to examine whether midbrain GAB A (A) and (B) receptor systems modulate mesolimbic dopamine during the two phases of alcohol drinking behavior: seeking and consumption. Together these two components regulate alcohol intake and although certain aspects of their function may overlap in humans, they can be studied independently in a rodent model. Mesolimbic pathways from the ventral tegmental area to the nucleus accumbens (NAc) and central nucleus of the amygdala (Amg) have a major role in regulating both the motivational and consummatory behaviors related to alcohol use. However, changes in the level of mesolimbic dopamine in these brain regions have only been investigated during the drinking phase. Extracellular levels of dopamine will be evaluated in the nucleus accumbens and central nucleus of the amygdala.
Aim 1 (rats and mice) will characterize the pattern of change of dopamine during ethanol seeking and consumption.
Aim 2 (rats) will examine the role of GABA (A) and (B) receptor agonist effects on dopamine levels during ethanol seeking and consumption.
Aim 3 will examine dopamine levels in GABA (A) receptor alpha knockout mice during alcohol seeking and consumption. The mentoring team will be comprised of leaders in alcohol and addiction research and the proposed research and career development plan will provide extensive training including the theoretical and practical aspects of operant conditioning, and utilization of in vivo microdialysis and HPLC for the assessment of extracellular dopamine levels in an across species paradigm. This novel approach will characterize the circuitry and specific neurotransmitter systems involved in ethanol-directed behaviors. These findings may lead to a pharmacological treatment that will attenuate alcohol """"""""craving"""""""" and alcohol drinking. The project will assess the motivational and reinforcing aspects of alcohol underlying neurocircuitry and receptor mechanisms that will recipitate the planning of an RO1.
| Fitzgerald, Devon M; Charness, Michael E; Leite-Morris, Kimberly A et al. (2011) Effects of ethanol and NAP on cerebellar expression of the neural cell adhesion molecule L1. PLoS One 6:e24364 |
