Effects of kappa-opioid receptor stimulation on addiction-related behavior in female rats: differences along the rostro-caudal axis of the nucleus accumbens shell

Rationale: Affective behavioral effects of kappa-opioid receptor (KOR) stimulation have been found to vary between the rostral and caudal nucleus accumbens (NAc) shell, but this has so far only been demonstrated in males. Objectives: To examine the effects of KOR activation in subregions of the NAc shell on affective and motivated behavior in females. Methods: In one group of Long-Evans rats, females were given access to 20% ethanol in an intermittent-access procedure and then injected within-subject with the selective KOR agonist, U50,488, or vehicle in the rostral or caudal NAc shell, prior to being tested in a light-dark box or having their ethanol drinking monitored. In a second group of Long-Evans rats, females and males were trained to self-administer 10% sucrose and then injected within-subject with U50,488 or vehicle in the rostral or caudal NAc shell, prior to being tested in a progressive ratio (PR) schedule of reinforcement. Results : Injection of U50,488 into the caudal but not rostral NAc shell reduced the number of entries into the light chamber of a light-dark box, while injection of U50,488 into the rostral but not caudal NAc shell reduced ethanol drinking. Injection of U50,488 into neither the rostral nor the caudal NAc shell had any effect on any measure of sucrose intake. Conclusions: The present findings confirm and extend previous findings regarding the effects of KOR activation in subregions of the NAc shell on affective and motivated behavior. These results support a continued focus on the KOR as a possible pharmacotherapeutic target.