| Abstract: |
Previous studies have demonstrated that morphine inhibits the display of maternal behavior in lactating rats. Whether morphine exerts its actions specifically at the mu receptor has not yet been determined. The present study examined this possibility by evaluating whether naloxonazine, an irreversible and selective antagonist of the mu1 opioid receptor subtype, is able to attenuate morphine's disruptive effect on maternal behavior in primiparous lactating rats. Experiment 1 compared the ability of naloxonazine (AZINE) and naloxone (NAL) to block the action of morphine (MOR) on maternal care. Virgin, Sprague-Dawley rats were mated in our colony and on day 3 postpartum (parturition, day 0) all rats received jugular catheters. On day 6 the mothers received one of the following treatments: MOR alone (10 mg/kg, SC, N=10); MOR (10 mg/kg, SC) 24 hr after AZINE pretreatment (10 mg/kg, IV, N=10); MOR (10 mg/kg, SC) 24 hr after NAL pretreatment (10 mg/kg, IV, N=8); or MOR (10 mg/kg, SC) immediately after NAL (0.5 mg/kg, SC, N=10). MOR alone completely disrupted maternal behavior (0% responded) which was blocked by prior NAL administration (100%). AZINE pretreatment 24 hr earlier partially blocked MOR disruption of MB (40% responded; significantly different from MOR alone). The response of rats pretreated 24 hr earlier with NAL did not differ from MOR alone. AZINE blocked MOR's effect on pup retrieval to an even greater degree (70% responded vs. 10% in MOR alone). Experiment 2 determined the ability of AZINE to interfere with varying doses of MOR on maternal behavior. A separate group of female rats was mated and catheterized on postpartum day 3. On day 5 half the rats received vehicle while the other half AZINE (10 mg/kg, IV). On day 6 all the rats received MOR (SC) at one of the following doses: 2.5, 5.0, 7.5, 10, or 12.5 mg/kg. MOR disrupted full maternal behavior and retrieval in a dose-dependent fashion. Pretreatment with AZINE significantly shifted MOR's full maternal behavior and retrieval dose response curves 1.5-fold and 1.4-fold to the right, respectively. These data indicate that opioid disruption of maternal behavior is mediated, in part, by the mu1 opioid receptor system. © 1990. |
| Keywords: |
nonhuman; animal; animal experiment; psychological aspect; rat; pregnancy; rats; morphine; mu opiate receptor; receptors, opioid, mu; naloxone; behavior, animal; naloxonazine; opioid receptors; rats, inbred strains; subcutaneous drug administration; receptors, opioid; female; priority journal; article; maternal behavior; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; mu1-binding site
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