BEHAVIORAL PREDICTORS OF INDIVIDUAL DIFFERENCES IN OPIOID ADDICTION VULNERABILITY

Abstract

Understanding behavioral predictors of individual differences in opioid addiction vulnerability could provide critical insights into the mechanisms underlying opioid addiction and could lead to more effective treatments. However, very few behavioral predictors of individual differences in opioid self-administration (SA), a key preclinical model of opioid addiction, have been established. The goal of this dissertation was to evaluate several potential behavioral predictors of individual differences in morphine SA in rats, and to establish novel methodologies for studying opioid addiction vulnerability using the SA paradigm. Study 1 showed that spontaneous locomotor activity in a novel environment, an animal model of sensation-seeking that predicts SA of several drugs of abuse (e.g., stimulants), did not predict individual differences in morphine SA. Study 2 found that greater severity of anhedonia-like behavior during withdrawal from acute morphine exposure (withdrawal-induced anhedonia, WIA) predicted subsequent lower acquisition, demand, and reinstatement of morphine SA. Study 3 showed the feasibility of using regularized factor analysis on morphine SA measures, and revealed that a common latent factor underlies four separate measures of morphine SA. Additionally, while acquisition, demand and morphine-induced reinstatement associated closely with the common latent Addiction factor, stress-induced reinstatement did not. Overall, these studies extended the opioid individual differences literature by establishing WIA as one of the first behavioral predictors of opioid SA, and also expanded the range of analytical tools to be utilized in preclinical behavioral studies.