Endogenous opioids: do they modulate the rat pup's response to social isolation?

Previous studies with several different species have suggested that opioids and their receptors are involved in the mediation of the infant's vocal response to social isolation. In the case of the rat pup, 2 models have been hypothesized to relate opioids and the ultrasonic call emitted during social isolation. One model views the comforting effects of social contact as opioid mediated and the apparent distress of social isolation as analogous to opiate withdrawal. The 2nd model considers social separation as a stressor that recruits endogenous opioids. This article describes 3 experiments that tested both of these models in 7-10-day-old rat pups. In Experiment 1, morphine (0.04-0.40 mg/kg) decreased the rate of isolation calls in a dose-dependent, naloxone-reversible fashion. However, the decrease in calling rate was observed only at doses that decreased locomotor activity. Administration of the reversible opiate antagonist naloxone (0.05-5.0 mg/kg) did not alter the rate of calls during either 2- or 6-min isolation tests at either 24 or 32 degrees C. In Experiment 2, the irreversible mu opioid receptor antagonist beta-funaltrexamine (beta-FNA) was administered into the lateral ventricle of 6-day-old pups. Again, no change in the rate of isolation calls was found, although sensitivity to morphine was markedly decreased, and mu (but not delta or kappa) receptors were decreased in selected brain regions by about 40%. In Experiment 3, in vivo receptor binding was used to directly investigate the availability of mu opioid receptors during social contact and social isolation. Pups injected with 3H-diprenorphine showed relatively high levels of specific in vivo binding that followed the regional pattern of in vitro binding, but no effects of social isolation were apparent in the 5 brain regions assayed. Taken together, the consistent negative results with opiate receptor antagonists, as well as the inability to detect an alteration of in vivo binding, suggest that the mu opioid receptor is not an essential part of the rat pup's vocal response to social separation.