Delta opioid receptors: reflexive,defensive and vocal effective responses in female rats

Ultrasonic vocalizations may be an expression of the affective pain response in laboratory animals. The present experiment compares the effects of morphine to the delta agonist, DPDPE (d-Pen²,d-Pen⁵ enkephalin) on a range of reflexive, behavioral and affective responses during an aggressive interaction. In experiment 1, naive female Long-Evans rats received morphine (0, 1, 3, 6, 10 µg ICV), or DPDPE (0, 30, 60, 100 µg ICV). In experiment 2, female rats were treated with naltrindole (1.0 mg/kg IP) 20 min before DPDPE (0, 60, 100 µg ICV). The following endpoints were measured: (1) latency to tail flick in response to heat stimuli; (2) high (33–65 kHz) and low (20–32 kHz) frequency ultrasonic and audible vocalizations; (3) defensive behavior; and (4) motoric activity. Following a brief exposure to attack, rats were threatened by the aggressor but protected from further attack by a large, wire mesh cage, thereby allowing for continued behavioral and vocal measurement without the risk of physical injury; video and audio recordings were made during the attack and then during a portion of the protected encounter (2 min). Morphine suppressed pain reactions varying in complexity from a spinal reflex, to an organized escape reaction, to an affective vocal response. The delta agonist, DPDPE, attenuated high frequency ultrasonic calling and tail flick responding. Defensive behaviors were also modulated by DPDPE at doses that had no effect on walking or rearing, indicating behavioral specificity. By contrast, doses of morphine that decreased defensive upright and escape also decreased motor activity. In female rats, morphine and DPDPE share a common profile of effects on a range of functional end-points, but DPDPE appears to modulate more selectively the reactions related to aversiveness without exerting sedative effects. These data demonstrate a possible physiological role for delta receptors in affective and defensive reactions.