μ-Opioid blockade reduces ethanol effects on intake and behavior of the infant rat during short-term but not long-term social isolation

Abstract

Numerous findings in adult and infant rats have shown that the endogenous opioid system is involved in control of ethanol consumption and its reinforcing effects. Opioid systems are also involved in reactivity to social isolation with several factors (age, duration, and type of isolation) affecting this modulation. The present study investigated the effects of a selective mu-opioid antagonist CTOP (0, 0.1, 0.5mg/kg), ethanol (0, 0.5 g/kg), and the interaction of the two drugs on the behavioral consequences of two types of social isolation given to preweanling rats: 1) short-term social isolation from littermates (STSI, duration 8 min) and 2) relatively long-term (5h) isolation (LTSI) from the dam and littermates. Voluntary intake of saccharin, locomotion, rearing activity, paw licking, and grooming were assessed during an 8-min. intake test. Thermal nociceptive reactivity was also measured before and after the testing session with normalized differences in pre- and post-test latencies of paw withdrawal from a hot plate (49°C) used as an index of isolation-induced analgesia (IIA). The results indicate that pharmacological blockade of mu-opioid receptors by CTOP substantially attenuated ethanol's anxiolytic effects on the developing rat's reactions to social isolation. Some of these stress-attenuating effects of CTOP were observed only in animals exposed to short-term isolation (STSI) but not in pups isolated for 5h (LTSI). Ethanol selectively increased saccharin intake during STSI in females and CTOP blocked this effect. Ethanol decreased the magnitude of analgesia associated with STSI but had no effect on pain reactivity during LTSI. CTOP by itself did not affect IIA or saccharin intake in sober animals. The findings of the present experiments indicate that the anxiolytic effects of 0.5 g/kg ethanol on pups exposed to STSI are modulated by endogenous opioid activity.