Suppression of ethanol responding by centrally administered CTOP and naltrindole in AA and Wistar rats

Background: Both mu- and delta -opioid receptors have been implicated in th e reinforcing actions of ethanol. However, selective opioid receptor antago nists have not altered ethanol intake in all rodent strains consistently, w hich suggests that genotype may modulate their suppressive effects. Therefo re, we tested the effects of the selective mu -antagonist D-Pen-Cys-Tyr-D-T rp-Orn-Thr-Pen-Thr-NH2 (CTOP) and the selective delta -antagonist naltrindo le in both high-drinking AA (Alko, Alcohol) and heterogeneous Wistar rats. Methods: AA and Wistar rats were trained to respond for ethanol (10% w/v) i n a two-lever operant condition by using a saccharin fading procedure. Afte r stable baseline responding was established, rats were implanted stereotax ically either with a guide cannula above the lateral ventricle or with bila teral cannulas above the nucleus accumbens, basolateral amygdala, or ventra l tegmental area. After postoperative recovery, AA and Wistar animals were tested after intracerebroventricular microinjections of either CTOP (0-3 mu g) or naltrindole (0-30 mug) or subcutaneous injections of naloxone (0-1 g/ kg), which was used as a reference antagonist. Effects of intracerebral mic roinjections of CTOP and naltrindole (both 0-500 ng) were tested only in Wi star rats. Results: Subcutaneous naloxone and intracerebroventricular CTOP and naltrin dole suppressed ethanol self-administration in a similar manner in AA and W istar rats. Cumulative response patterns indicated that naloxone and naltri ndole had no effect on the initiation of responding but suppressed it later during the session, whereas CTOP also affected initiation. In Wistar rats, naltrindole microinjections into both the nucleus accumbens and basolatera l amygdala decreased ethanol responding, whereas CTOP was effective only in the amygdala. Injections of these antagonists into the ventral tegmental a rea had little effect on ethanol intake. Conclusions: The results confirm previous results which showed that both mu - and delta -opioid receptors are involved in the regulation of ethanol sel f-administration and indicate that genetic differences between AA and Wista r rats produced by selection do not modify the effects of opioid antagonist s. The nucleus accumbens and the basolateral amygdala may be important cent ral sites for the mediation of their suppressive effects.