Role of alpha2A-adrenergic receptors in extinction of positive and negative valence learned behaviors

Abstract

NEUROSCIENCE

ROLE OF α2A ADRENERGIC RECEPTORS IN EXTINCTION OF POSITIVE AND NEGATIVE VALENCE LEARNED BEHAVIORS

Adeola R. Davis

Dissertation under the direction of Professor Danny Winder The work presented in this dissertation focuses on the role of α2 adrenergic receptors in extinction of positive and negative valence learned behaviors as well as investigating the mechanism of the action of a pharmaceutical agent, yohimbine. Mechanisms underlying extinction of positive valence associations such as drug self administration and place preference are poorly understood, yet may have important relevance to addiction treatment. Data suggest a major role for the noradrenergic system in extinction of fear-based learning. Administration of yohimbine, an α2 adrenergic receptor antagonist, facilitates extinction of learned fear. Employing a combination of pharmacological and genetic approaches, we investigated the role of the α2 adrenergic receptor in extinction of cocaine-induced conditioned place preference and lithium chloride-induced conditioned place aversion. Additionally, yohimbine is a commonly used pharmaceutical agent and the mechanism of action is often attributed to solely antagonism at the α2 adrenergic receptors. However, we investigate potential off target sites using electrophysiological methods. In this research, the results indicate that extinction of conditioned place preference with yohimbine occurs independently of the α2 adrenergic receptors although the receptors modify the effect. Further, extinction with yohimbine of conditioned place preference and conditioned place aversion similarly impairs extinction of the behaviors. Lastly, we found a novel target for extinction behaviors with the use of electrophysiology.