Microinjection of the δ-opioid receptor selective antagonist naltrindole 5′-isothiocyanate site specifically affects cocaine self-administration in rats responding under a progressive ratio schedule of reinforcement

Whether the δ-opioid receptor (DOR) system can modulate behavioral effects of cocaine remains equivocal. We examined whether site- and subtype-selective blockade of DORs within the rat mesocorticolimbic system affects cocaine self-administration. The DOR antagonist naltrindole 5′-isothiocyanate (5′-NTII; 5 nmol) was microinjected into the nucleus accumbens (NAcc), ventral tegmental area (VTA), or amygdala (AMYG) in rats self-administering 1.5 mg/kg cocaine under a progressive ratio (PR) schedule. Intra-NAcc 5′-NTII significantly decreased cocaine self-administration, while 5′-NTII administration into the VTA significantly increased cocaine-maintained responding. 5′-NTII administration into the AMYG produced no effect. These data support a site-specific role of DORs in cocaine's behavioral effects.