Effects of the δ‐opioid receptor antagonist naltrindole on antinociceptive responses to selective δ‐agonists in post‐weanling rats

Abstract

Antagonism, by the selective δ‐opioid receptor antagonist naltrindole, of the antinociceptive effects of [d‐Pen2, d‐Pen5] enkephalin (DPDPE), [d‐Ser2, Leu5, Thr6] enkephalin (DSLET) and d‐Ala2 deltorphin I (DELT I) has been studied in 25 day old rats. Antinociception was measured by the 50°C tail immersion test following i.p. administration of agonists and/or antagonists. Dose‐related antinociception was observed with DPDPE, DSLET and DELT I and ED75 doses were computed (0.66 mg kg−1, 0.65 mg kg−1, 0.032 mg kg−1 respectively) and used for antagonism studies. Naltrindole (0.01 mg kg−1) significantly attenuated the antinociceptive effects of DPDPE and DSLET with 0.1 mg kg−1 producing complete reversal of the effects of the ED75 dose. In contrast, naltrindole at 0.01 and 0.1 mg kg−1 did not alter antinociceptive responses to DELT I. Naltrindole at 1 mg kg−1 significantly attenuated DELT I antinociception. Naloxone (1 mg kg−1) produced equivalent degrees of antagonism of the antinociceptive effects of DPDPE, DSLET and DELT I. ICI 174,864 (1 mg kg−1) also antagonized antinociception with a differential degree of attenuation (DSLET > DPDPE > DELT I). 6 Naltrindole (1 mg kg−1) had no effect on the antinociception induced by the selective μ‐agonist alfentanil (60 μgkg−1). Naltrindole, naloxone or ICI 174,864 had no effect on nociceptive latencies. 7 The differential antagonism by naltrindole of the effects of three selective δ‐agonists suggests δ‐receptor heterogeneity. Further, the lower sensitivity of response to DELT I suggests that this agent may exert its antinociceptive effects at a different δ receptor subtype from DPDPE or DSLET. 1992 British Pharmacological Society