Less is known about potential anti-addictive properties of N/OFQ in relation to other drugs of abuse. It has been shown that N/OFQ prevents the expression of conditioned place preference for cocaine, methamphetamine and morphine (Ciccocioppo et al., 2000; Kotlinska et al., 2002; Murphy et al., 1999; Zhao et al., 2003). Accordingly, microdialysis experiments have shown that intracranial N/OFQ injections prevent cocaine- and morphine-induced increases in extracellular dopamine within the nucleus accumbens (Di Giannuario and Pieretti, 2000; Lutfy et al., 2001). Indirect evidence supporting the ability of N/OFQ to attenuate the rewarding effect of drugs of abuse also comes from studies on NOPR null-mutant mice, which had increased sensitivity to the rewarding effects of cocaine, morphine and nicotine (Marquez et al., 2008; Rutten et al.; Sakoori and Murphy, 2009). For a better assessment of their potential anti-addictive properties in relation to these drugs, however, NOPR agonists need to be examined using self-administration and reinstatement experiments. One study has examined the effects of N/OFQ on stress-induced reinstatement of cocaine seeking under operant conditions, and the results were negative (Martin-Fardon et al., 2000).
