No abstract

To determine whether benzodiazepines (BDZs) quiet isolation distress in 10-day-old rat pups by causing a release of endogenous opioids, a blockade of the effects of chlordiazepoxide (CDP) by the opiate antagonist naltrexone (NLX) was sought. Nonsedating doses of morphine (MOR) (0.125 mg/kg) and CDP (2.0 mg/kg) were equally effective in reducing ultrasonic vocalizations and other indices of isolation distress. Appropriate blocking agents NLX, (0.5 mg/kg) against MOR and Ro 15-1788 (4.0 mg/kg) against CDP returned distress measures to levels of salinetreated rat pups. However, NLX failed to reverse the quieting effects of CDP. If CDP potentiates endogenous opioid release, then NLX should block the CDP effect. A higher dose of CDP did not reveal a release of endogenous opioids, and a higher dose of NLX did not antagonize CDP. The quieting effects of BDZs on isolation distress do not appear to be mediated by the opiate system.

The presence of a single anesthetized littermate significantly reduced the rate of ultrasonic vocalization by 10-day-old pups isolated in a novel environment. Naltrexone (1.0 mg/kg) returned the vocalization rate to the level of pups tested alone and disrupted the maintenance of body contact between the test pup and a companion. This suggests that the companion exerts comforting effects through endogenous opioid mechanisms. Although chlordiazepoxide is as effective as morphine in the quieting of isolation distress, the benzodiazepine (BDZ) antagonist Ro 15-1788 (5, 10, or 20 mg/kg) was ineffective in blocking the comfort effect and facilitated quiet contact with the companion. In isolated pups, Ro 15-1788 caused a significant, but not a dose-related, decrease in vocalization, a possible indication of the displacement of an endogenous anxiogenic ligand at the BDZ receptor complex.

Separation-induced calling in the young of many species can be modulated by the opioid system. Morphine reduces ultrasonic vocalizations (USVs) produced by isolated rat pups, an effect blocked by naltrexone. Central administration of the mu and delta opiate receptor agonists DAMGO and DPDPE reduce USV; kappa receptor agonist U50,488 increases them. We now find that peripheral U50,488 not only boosted calling rates in isolated 3-, 10-, and 18-day-old rat pups, but also induced calling in pups of these ages tested in the home cage with their littermates, where USVs are seldom heard in nature. U50,488 lowered rectal temperature, although temperature loss and USV were not correlated within drug treatment groups.