Involvement of mu-opioid receptors in alcohol drinking by alcohol-preferring AA rats

The present study examined the role of mu- and delta-opioid receptors in alcohol drinking using antagonists selective for these receptor types. Food- and water-sated male and female AA (Alko, alcohol) rats consistently drank 10% alcohol during daily 30-min access periods in their home cages in the middle of the 12-h light phase. On 3 consecutive days, the animals received the mu-opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP, 1 micrograms ICv), the delta-receptor antagonist N,N-diallyl-Try-Aib-Aib-Phe-Leu-OH (ICI 174,864, 3 micrograms ICV), or saline 15 min before the alcohol access period. Relative to saline, the mu-antagonist CTOP decreased alcohol drinking both by males and females progressively over the 3 treatment days, with a continued suppression on the first days after the termination of the administration. Treatment with the delta-antagonist ICI 174,864 had no effect on alcohol drinking in males, and produced transient hind limb dysfunction and barrel rolling in over half of the females. These results suggest that selective blockage of mu-opioid receptors is sufficient to suppress alcohol drinking in AA rats.