EFFECTS OF MU-OPIOID AND DELTA-OPIOID AGONISTS AND ANTAGONISTS ON AFFECTIVE VOCAL AND REFLEXIVE PAIN RESPONSES DURING SOCIAL STRESS IN RATS

The present experiments evaluated the influence of intraventricular mu and delta opioid receptors on affective vocal and reflexive responses to aversive stimuli in socially inexperienced, as well as defensive a nd submissive responses in defeated, adult male Long-Evans rats. Defea t stress consisted of: (1) an aggressive confrontation in which the ex perimental intruder rat exhibited escape, defensive and submissive beh aviors [i.e., upright, supine postures and ultrasonic vocalizations (U SV)], and subsequently, (2) protection from the resident stimulus rat with a wire mesh screen for 10-20 min. Defeat stress was immediately f ollowed by an experimental session with tactile startle (20 psi), The mu opioid receptor agonists morphine (0.1-0.6 mu g ICV) and [D-Ala(2)- N-Me-Phe(4)-Gly(5)-ol]-enkephalin (DAMGO; 0.01-0.3 mu g ICV), and the delta opioid receptor agonist [D-Pen(2,5)]-enkephalin (DPDPE; 10-100 m u g ICV) dose-dependently decreased startle-induced USV and increased tail-flick latencies in socially inexperienced and defeated rats. Of g reater interest, morphine, DAMGO and DPDPE increased the occurrence of the submissive crouch posture, and defeated rats were more sensitive than socially inexperienced rats to the startle-induced USV-suppressiv e and antinociceptive effects of morphine and DPDPE. The antinocicepti ve effects of DAMGO were likewise obtained at lower doses in defeated rats. Finally, the USV-suppressive effects of morphine and DAMGO were reversed with the mu receptor antagonist naltrexone (0.1 mg/kg IP), bu t the USV-suppressive effects produced by DPDPE were not reversed with the delta receptor antagonist naltrindole (1 mg/kg IP). These results confirm mu, but not delta opioid receptor activation as significant i n affective vocal, passive-submissive behavior, as well as reflexive a ntinociception. Furthermore, similar to previous studies with restrain t and electric shock stress, the facilitation of mu opioid effects on vocal responses and antinociception is consistent with the proposal th at defeat stress activated endogenous opioid mechanisms.