Opioid stimulation in the ventral tegmental area facilitates the onset of maternal behavior in rats

This research investigated the effect of an increase or decrease in opioid activity in the ventral tegmental area (VTA) on the onset of maternal behavior in rats. In Experiment 1, the latency to show maternal behavior toward foster rat pups (sensitization latency) was determined in maternally naive female rats given either nothing or a unilateral intra-VTA injection of morphine sulfate (MS) (0.0, 0.01, 0.03, 0.1 or 0.3 µg), on the first three days of a 10-day period of constant exposure to pups. Rats treated with 0.03 µg MS had significantly shorter sensitization latencies than did rats treated with 0.0 µg MS, 0.01 µg MS, or receiving no treatment (higher doses of morphine produced intermediate results). The facilitating effect of intra-VTA MS on the onset of maternal behavior was blocked by pretreatment with naltrexone hydrochloride and was found to have a specific site of action in the VTA (MS injections dorsal to the VTA were ineffective). In Experiment 2, sensitization latencies were determined in periparturitional rats given a bilateral intra-VTA injection of either the opioid antagonist naltrexone methobromide (quaternary naltrexone), its vehicle, a sham injection, or left untreated 40 min after delivery of the last pup. The mothers' own pups were removed at delivery; mothers were nonmaternal at the time of testing. Quaternary naltrexone treatment produced significantly slower sensitization to foster pups than did control conditions. Total activity and pup-directed activity did not differ significantly with treatment. The results demonstrate that increased opioid activity in the VTA facilitates the onset of maternal behavior in inexperienced nonpregnant female rats, and decreased opioid activity in the VTA disrupts the rapid onset of maternal behavior at parturition

Enhancement of Opioid-Mediated Analgesia\ud by Ingestion of Amniotic Fluid:\ud Onset Latency and Duration

Ingestion of placenta and amniotic fluid has been shown to enhance opioid-mediated analgesia produced by morphine injection, footshock, vaginal/cervical stimulation, and during late pregnancy in rats. The present study was designed to determine how soon after ingestion the enhancement begins and how long it lasts. Tail-flick latencies in Long-Evans rats were determined before and during vaginal/cervical stimulation; analgesia was measured as the percent increase in tail-flick latency during vaginal stimulation. After determination of baseline, rats were intubated with 0.25 ml of either amniotic fluid or beef bouillon. We found that analgesia enhancement was detectable as early as 5 minutes after ingestion of amniotic fluid, and the effect lasted at least 30 minutes, but no longer than 40 minutes

Placentophagia in Nonpregnant Rats:\ud Influence of Estrous Cycle Stage and Birthplace

Prior parturitional experience and genotype have previously been found to affect the proportion of nonpregnant female rats and mice that will eat foster placenta. The present series of experiments was designed to investigate the influence of estrous cycle stage on placentophagia in rats. Foster placenta was presented to nonpregnant Long-Evans females, purchased from a commercial breeder, for 15 min on 5 consecutive days. We found that virgin placentophages were most likely to have eaten placenta on the first presentation, unless the first presentation occurred during proestrus. In fact, virgins would not eat placenta for the first time during proestrus, regardless of test-day. However, once they had eaten placenta, either in a nonproestrus stage, or, in the case of primiparae, during parturition, they would eat placenta during proestrus. Long-Evans rats born in our laboratory differed from the purchased rats, manifesting an incidence of placentophagia that was too low to be analyzed by stage of the estrous cycle; when tested as primiparae, however, there were no differences between the two groups

Amniotic-Fluid Ingestion Enhances\ud Morphine Analgesia During Morphine\ud Tolerance and Withdrawal in Rats

Ingestion of placenta and amniotic fluid has been shown to enhance opioid-mediated analgesia in rats produced by morphine injection. footshock, vaginal/cervical stimulation, and during late pregnancy. The present study was designed to investigate the effects of amniotic fluid ingestion on the characteristics of morphine dependency and withdrawal. Tail-flick latencies in Long-Evans rats were determined before and after repeated daily injections of morphine sulfate. It was found that ingestion of amniotic fluid after establishment of the morphine dependency, coupled with an injection of an otherwise ineffective dose of morphine, enhanced analgesia in morphine-dependent rats, and reversed hyperalgesia seen during withdrawal from morphine dependency

Ingestion of Amniotic Fluid Enhances\ud Opiate Analgesia in Rats

Placenta ingestion has recently been shown to enhance opiate-mediated analgesia produced by morphine injection, footshock, or vaginal/cervical stimulation. The enhancement of the effect of endogenous opiates (especially analgesia) may be one of the principal benefits to mammalian mothers of placentophagia at delivery. During labor and delivery, however, mothers also ingest amniotic fluid (AF) which, unlike placenta, becomes available during, or even before expulsion of the infant. The present experiments were undertaken to determine (a) whether AF ingestion, too, enhances analgesia; if so, (b) whether the effect requires ingestion of, or merely exposure to, AF; (c) whether the effect can be produced by AF delivered directly to the stomach by tube; and (d) whether the enhancement, if it exists, can be blocked by administering an opiate antagonist. Nulliparous Long-Evans rats were tested for analgesia using tail-flick latency. We found that (a) rats that ingested AF after receiving a morphine injection showed significantly more analgesia than did rats that ingested a control substance;' (b) AF ingestion, alone, did not produce analgesia; (c) ingestion of AF, rather than just smelling and seeing it, was necessary to produce analgesia enhancement; (d) AF produced enhancement\ud when oropharyngeal factors were eliminated by delivering it through an orogastric tube; and (e) treatment of the rats with naltrexone blocked the enhancement of morphine-induced analgesia that results from AF ingestion

Dose-Dependent Enhancement of Morphine-Induced Analgesia\ud by Ingestion of Amniotic Fluid and Placenta

Ingestion of amniotic fluid and placenta by rats has been shown to enhance opioid-mediated analgesia. The present studies were designed to examine the effect of several doses and volumes of placenta and amniotic fluid on tail-flick latency in rats treated with 3 mg/kg morphine. The optimal dose of amniotic fluid was found to be 0.25 ml, although 0.50 and 1.0 ml also produced significant enhancement. Doses of 0.125 and 2 ml of amniotic fluid were ineffective, as was a dose of 0.25 ml diluted to 2 ml with saline. The optimal dose of placenta was found to be 1 placenta, although the resulting enhancement was not significantly greater than that produced by 0.25, 0.50, 2.0 or 4.0 placentas. Doses smaller than 0.25 placenta or larger than 4.0 placentas were ineffective. The most effective doses of amniotic fluid and placenta correspond to the amounts delivered with each pup during parturition

Amniotic-Fluid Ingestion Enhances the Central\ud Analgesic Effect of Morphine

Amniotic fluid and placenta contain a substance (POEF) that when ingested enhances opioid-mediated analgesia produced by several agents (morphine injection, vaginal/cervical stimulation, late pregnancy, footshock), but not that produced by aspirin injection. The present series of experiments employed quaternary naltrexone, an opioid antagonist that does not readily cross the blood-brain barrier, in conjunction with either peripheral or central administration of morphine, to determine whether amniotic-fluid ingestion (and therefore POEF ingestion) enhances opioid-mediated analgesia by affecting the central and/or peripheral actions of morphine. The results suggest that POEF affects only the central analgesic effects of morphine

Ingested bovine amniotic fluid enhances morphine antinociception in rats

Ingestion by rats of rat placenta or amniotic fluid enhances opioid-mediated, or partly opioid-mediated, antinociception produced by morphine injection, vaginal or cervical stimulation, late pregnancy, and foot shock. This phenomenon is believed to be produced by a placental\ud opioid-enhancing factor (POEF). Ingestion by rats of human or dolphin placenta has also been shown to enhance opioid antinociception, suggesting that POEF may be common to many mammalian species. We tested bovine amniotic fluid (BAF) for its capacity to enhance morphine antinociception in female Long-Evans rats, as determined by percentage change from baseline tail-flick latency in response to radiant heat, and we report that 0.50 mL BAF effectively enhanced morphine antinociception but did not by itself produce antinociception. The efficacy of POEF across species suggests that POEF may have been functionally (and structurally) conserved during evolution. Furthermore, the availability of POEF at parturition, as well as its ability to enhance pregnancy-mediated antinociception without\ud disrupting maternal behavior, offers a tenable explanation for the long-debated ultimate causality of placentophagia

Ingested placenta blocks the effect of morphine on gut transit in Long–Evans rats

Opioids produce antinociception, and ingested placenta or amniotic fluid modifies that antinociception. More specifically, ingested placenta enhances the antinociception produced by selective activation of central n-opioid or y-opioid receptors but attenuates that produced by activation of central A-opioid receptors. Opioids also slow gut transit by acting on central or peripheral A-opioid receptors. Therefore, we hypothesized that ingested placenta would reverse the slowing of gut transit that is produced by morphine, a preferential A-opioid-receptor agonist. Rats were injected with morphine either centrally or systemically and fed placenta, after which gastrointestinal transit was evaluated. We report here that ingested placenta reversed the slowing of gut transit produced by centrally administered morphine but did not affect the slowing of gut transit produced by systemically administered morphine. These results suggest another likely consequence of placentophagia at parturition in mammals—reversal of opioid-mediated, pregnancy-based disruption of gastrointestinal function—as well as an important consideration in opioid-based treatments for pain in humans—enhancement of desirable effects with attenuation of adverse effects

Placenta Ingestion Enhances Analgesia\ud Produced by Vaginal/Cervical\ud Stimulation in Rats

Ingestion of placenta has previously been shown to enhance opiate-mediated analgesia (measured as tail-flick latency) induced either by morphine injection or by footshock. The present study was designed to test whether placenta ingestion would enhance the partly opiate-mediated analgesia produced by vaginal/cervical stimulation. Nulliparous Sprague-Dawley rats were tested for analgesia, using tail-flick latency, during and after vaginal/cervical stimulation; the tests for vaginal/cervical stimulation-induced analgesia were administered both before and after the rats ate placenta or ground beef. Placenta ingestion, but not beef ingestion. significantly heightened vaginal/cervical stimulation-induced analgesia. A subsequent morphine injection provided evidence that, as in a previous report, placenta ingestion, but not beef ingestion, enhanced morphine-induced analgesia