Component #1

Pharmacotherapy and Medications of Ethanol Dependence and Relapse Drinking

Principal Investigator: William (Tripp) Griffin, Ph.D.
Co-Principal Investigator: Howard Becker, Ph.D.

Advances in our understanding of mechanisms underlying motivation to drink and, in particular, mechanisms that drive the transition from moderate drinking to more excessive and uncontrolled drinking are key to developing new and more effective treatment strategies. A contemporary view of alcohol addiction is that adaptations in glutamate (GLU) and dopamine (DA) transmission within regions of the striatum (key components of neurocircuitry that mediate motivated behavior) play a significant role in regulation of alcohol drinking behavior. While our current research efforts have focused on neurochemical adaptations in the ventral striatum (i.e., nucleus accumbens), recent evidence suggests that adaptations in GLU and DA transmission in the dorsolateral striatum (DLS) may play a prominent role in mediating the transition from controlled drinking to uncontrolled compulsive drinking that is characteristic of alcohol dependence.

The overall objective of this component is to examine adaptations in GLU and DA transmission in dorsal striatum that may qualitatively or quantitatively differ from those in ventral striatum, as well as evaluate the influence of pharmacotherapeutics on voluntary drinking and neurochemical alterations that may underlie motivation to drink in dependent compared to nondependent animals. This research uses an established animal model of alcohol dependence and relapse drinking, developed by the Becker lab, along with in vivo microdialysis procedures to characterize changes in extracellular levels of GLU and DA in dorsal compared to ventral regions of the striatum, that are associated with escalation of voluntary drinking in dependent animals compared to stable intake exhibited by nondependent animals.

Additionally, these studies will provide new information on potential neuroanatomical sites and neurochemical mechanisms underlying the ability of pharmacological treatments to reduce excessive drinking associated with dependence, which could lead to new insights and approaches in the development of more effective pharmacotherapies for the treatment of alcoholism.