Mood Alterations and Rewarding Properties

The mechanisms by which opioids produce euphoria, tranquility, and other alterations of mood (including rewarding properties) are not entirely clear. Behavioral and pharmacological evidence points to the role of dopaminergic pathways, particularly involving the nucleus accumbens (NAcc), in drug-induced reward.

The shell of the NAcc is the site that may be involved directly in the emotional and motivational aspects of drug-induced reward. All three opioid receptor types are present on the NAcc and are thought to mediate, at least in part, the motivational effects of opiate drugs.^[5] Selective μ- and δ-receptor agonists are rewarding when defined by place preference and intracranial self-administration paradigms. Conversely, selective κ-receptor agonists produce aversive effects. Positive motivational effects of opioids are partially mediated by dopamine release at the level of the NAcc.

The locus caeruleus contains both noradrenergic neurons and high concentrations of opioid receptors and is postulated to play a critical role in feelings of alarm, panic, fear, and anxiety. Neural activity in the locus caeruleus is inhibited by both exogenous opioids and endogenous opioid peptides.