Effect of Heroin and Heroin Conditioned Stimuli on Memory Consolidation

Abstract

It has been proposed that addictive substances and their associated stimuli enhance memory consolidation by activating central monoaminergic systems, but recent evidence suggests that these effects may be dependent on type of drug, dose, and how the drug is administered. The current dissertation tested the overarching hypothesis that heroin and heroin conditioned stimuli (CSs) modulate memory consolidation via a dopamine dependent signal of prediction. A series of studies were performed in male Sprague-Dawley rats using an object location memory task to explore the effect of various doses of heroin passively received (subcutaneous & intravenous) and self-administered (intravenous) on object location memory consolidation. As well, we investigated whether mode of administration could also impact the ability of different drug associated CSs to modulate memory consolidation at various stages of exposure in the absence of heroin. Finally, we examined whether memory modulation by heroin and heroin CSs involve a dopamine-dependent mechanism of prediction error. It was found that: 1) memory modulation by heroin was mediated by mode of drug administration and was affected by antagonism of the dopamine D1 receptor; 2) heroin’s facilitatory effect on memory only occurred when drug naïve rats were well habituated; and 3) a variety of heroin CSs (e.g., contextual and discrete) enhanced memory consolidation, regardless of mode of administration. The work presented in this dissertation provides novel insight about why, and how, unconditioned and conditioned opioid reinforcers impact cognition, and proposes the novel hypothesis that the enhancing function of drug reinforcers is modulated by their anticipated effects.