Long-term effects of parity on opioid and nonopioid behavioral and endocrine responses

Abstract

Parity (number of parturitions) affects the endogenous opioid system. Multiparous lactating rats are less sensitive to the effects of morphine (MOR) on maternal behavior (MB) and analgesia than primiparous lactating rats. In order to determine whether these changes in opiate sensitivity persist beyond the lactational state, the present study compared the sensitivity of ovariectomized nulliparous and nonlactating primiparous rats to MOR's effects on MB (Experiment 1), analgesia (Experiment 2) and prolactin release (Experiment 3) in addition to stress-induced analgesia (Experiment 2). In Experiments 1 and 2 primiparous rats were allowed to give birth and remain with their litter (culled to 6 pups) until weaning. At that time the pups were removed and the dams and age-matched nulliparous rats were ovariectomized. Four weeks later animals were exposed to foster pups daily in order to induce MB (Experiment 1). On day 5 or 6 of full MB the primiparous and nulliparous rats received either saline or one of four doses of MOR (0.625, 1.25, 2.5, or 5.0 mg/kg, SC) and 60 min later MB was assessed. MOR, at the 2.5 mg/kg dose, disrupted MB in a significantly greater percentage of nulliparous as compared to primiparous animals (100% vs. 55%, respectively). In Experiment 2, nulliparous and nonlactating primiparous animals received 2.5 mg/kg of MOR four weeks after ovariectomy. Analgesia was assessed on a tail-flick apparatus 30, 60, 90, 120 and 150 min postinjection. One week later the same animals were exposed to cold-water swims (CWS, 2°C, 3.5 min) and tail-flick latencies were again recorded. No differences were found between nulliparous and primiparous animals in either MOR or CWS analgesia. In Experiment 3, prolactin responses to MOR were measured in primiparous rats 5 weeks after their pups were weaned and in age-matched nulliparous animals. Each ovariectomized animal received 2 doses of MOR (2.5 and 10 mg/kg, IV) and saline over a 96-hr period. Blood samples were collected 10 and 0 min before and 5, 15, 30, 60 and 120 after injection. Although MOR stimulated prolactin release in both groups, no differences were found in MOR-induced prolactin release between nulliparous and primiparous ovariectomized rats. These data suggest that reproductive experience (pregnancy and lactation) has selective long-term effects on the endogenous opioid system reducing the sensitivity of the reproductively experienced female to MOR disruption of MB, but failing to affect MOR-induced analgesia and prolactin release as well as stress-induced analgesia.