Biomedical subjects

M B Kristal

Publications and source records attributed to M B Kristal.

At least 19 recordsLinked to original sources

PubMed1992

Gastric vagotomy blocks opioid analgesia enhancement produced by placenta ingestion.

Ingestion of amniotic fluid or placenta by rats has been shown to enhance opioid-mediated analgesia induced by morphine injection, footshock, vaginal/cervical stimulation, or late pregnancy. This enhancement by ingestion appears to be specific to the central actions of opioids. The present study was designed to examine the possibility that information traveling via the vagus nerve might be involved in mediating this effect. Rats that had undergone either selective gastric vagotomy or sham vagotomy were injected with either morphine sulfate or vehicle and fed either placenta or a meat control. Enhancement was observed in rats that had undergone sham vagotomy but not in those that had undergone gastric vagotomy. These results support an interpretation of vagal involvement in the enhancement of opioid-mediated analgesia by placenta.

Analgesia↗

PubMed1991

Maintenance and decline of the suppression of infanticide in mother rats.

Virgin female rats kill foster neonates, whereas newly parturient mothers do not. We demonstrated previously that this tendency to kill is suppressed shortly prepartum, presumably by physiological factors. In this study, we show that a) suppression of infanticide is maintained through the first two weeks of lactation; b) the mothers that do not kill foster neonates are not necessarily the same mothers that respond maternally toward older foster pups, and those that kill neonates are not necessarily the same ones that are nonmaternal to older pups, the two behaviors being somewhat independent; and c) some virgins can be induced to be noninfanticides by prolonged exposure to young, but only under special testing conditions not required by actual mothers, which are nonkillers of foster young. This suggests that the maintenance of the suppression of infanticide in mothers owes something to the special circumstances of lactation other than continued exposure to young.

Animals↗

PubMed1991

Placental opioid-enhancing factor (POEF): generalizability of effects.

A substance in amniotic fluid and placenta (POEF for Placental Opioid-Enhancing Factor) has been shown to enhance opiate- or opioid-mediated analgesia in rats. Recent studies have only touched on the generalizability of the phenomenon. The present studies further tested the generalizability of the POEF effect: they examined sex specificity of the mechanism; whether POEF activity exists in afterbirth material of species other than the rat; whether POEF activity exists in tissue other than afterbirth material; whether POEF activity could be demonstrated after injection rather than ingestion of afterbirth material; and whether POEF enhances all opioid-mediated phenomena. We found that (a) POEF is effective in male rats as well as in female rats; (b) POEF activity exists in human and dolphin afterbirth material; (c) ingestion of pregnant-rat liver does not produce enhancement of opioid-mediated analgesia; (d) POEF does not seem to be effective when amniotic fluid is injected either IP or SC; and (e) POEF does not modify morphine-induced hyperthermia.

Animals↗

PubMed1991

Amniotic fluid ingestion before vaginal/cervical stimulation produces a dose-dependent enhancement of analgesia and blocks pseudopregnancy.

A substance in amniotic fluid (AF) and placenta has been shown to enhance analgesia produced by morphine, late pregnancy, footshock, and vaginal/cervical stimulation (VS). When morphine-induced analgesia was assessed previously, the degree of enhancement by ingestion of AF or placenta was found to be a function of the amount of analgesia being generated. We have extended these results to include the analgesia produced by VS. Analgesia induced by 75, 125, 175, or 225 g of vaginal/cervical pressure was measured in rats pretreated with 0.25 ml (by orogastric infusion) of either AF or saline. AF infusion enhanced the analgesia produced by 125 g VS, but did not affect the analgesia produced by 75, 175, or 225 g VS. Unexpectedly, we also found that infusion of AF shortly before the application of VS prevents VS-induced pseudopregnancy (PsP). Whereas the incidence of PsP following 75, 125, or 175 g VS was less than 19% and not statistically different for AF and saline pretreatments, the incidence of PsP after 225 g VS was 44% in saline-pretreated rats, but only 10% in AF-pretreated rats. Protection from the induction of pseudopregnancy, which could be caused by mechanical stimulation of the cervical area during delivery, may be an additional benefit of parturitional ingestion of placenta and amniotic fluid (placentophagia).

Afferent Pathways↗

PubMed1991

Amniotic-fluid ingestion enhances morphine analgesia during morphine 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.

Amniotic Fluid↗

PubMed1991

Amniotic-fluid ingestion enhances the central 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.

Amniotic Fluid↗

PubMed1991

Enhancement of opioid-mediated analgesia: a solution to the enigma of placentophagia.

Two major consequences of placentophagia, the ingestion of afterbirth materials that occurs usually during mammalian parturition, have been uncovered in the past several years. The first is that increased contact, associated with ingesting placenta and amniotic fluid from the surface of the young, causes an accelerated onset of maternal behavior toward those young. The second, which probably has importance for a broader range of mammalian taxa than the first, is that ingestion of afterbirth materials produces enhancement of ongoing opioid-mediated analgesia. The active substance in placenta and amniotic fluid has been named POEF, for Placental Opioid-Enhancing Factor. Recent research on both consequences is summarized, with particular attention to POEF, the generalizability of the enhancement phenomenon, its locus and mode of action, and its significance for new approaches to the management of pain and addiction.

Analgesia↗

PubMed1990

Amniotic-fluid ingestion by parturient rats enhances pregnancy-mediated analgesia.

Amniotic fluid and placenta contain a substance (POEF, for Placental Opioid-Enhancing Factor) that, when ingested, enhances opioid-mediated analgesia in nonpregnant rats; ingestion of the substance by rats not experiencing opioid-mediated analgesia, however, does not produce analgesia. It is highly likely that periparturitional analgesia-enhancement is a significant benefit of ingestion of the afterbirth (placentophagia) during delivery. Here we report that prepartum ingestion of amniotic fluid (via orogastric infusion) does indeed enhance the endogenous-opioid-mediated analgesia evident at the end of pregnancy and during delivery; that the degree of enhancement is greater with 0.75 ml than with 0.25 ml; and that the prepartum enhancement of analgesia can be blocked with the opioid antagonist naloxone.

Amniotic Fluid↗

PubMed1990

Amniotic fluid ingestion enhances opioid-mediated but not nonopioid-mediated analgesia.

Ingestion of amniotic fluid or placenta by rats has been shown to enhance several types of opioid-mediated analgesia: that induced by morphine, footshock, vaginal/cervical stimulation, and late pregnancy. This enhancement has also been blocked by administration of opioid antagonists. The present study was designed to examine further the specificity of the enhancement effect for opioid-mediated analgesia by testing for enhancement following administration of aspirin, a nonopioid analgesic. The formalin test was used as the pain threshold assay. Amniotic fluid or beef bouillon was administered by orogastric tube to rats that were treated either with morphine sulfate or saline, or pretreated with naltrexone, then treated with aspirin or vehicle. Both morphine and aspirin treatments produced analgesia. Amniotic fluid significantly enhanced the analgesia produced by morphine, but did not enhance the analgesia produced by aspirin, further suggesting that the enhancing effect of amniotic fluid ingestion is specific for opioid-mediated analgesia, such as that existing at the start of parturition.

Amniotic Fluid↗

PubMed1990

An adaptable microcomputer program for recording behavior durations.

A versatile and easy to use program is described for monitoring and recording behavior durations on IBM-compatible microcomputers. The program also records frequencies and provides latency information. Among its more prominent attributes are its ability to accommodate a broad range of behavioral assays and the facility with which its operation can be mastered. It requires no specialized hardware and is capable of being used in conjunction with a number of commercially available software packages for statistical analysis.

Animals↗

PubMed1989

Enhancement of opioid-mediated analgesia by ingestion of amniotic fluid: 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.

Amniotic Fluid↗

PubMed1988

Dose-dependent enhancement of morphine-induced analgesia 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 025, 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↗

PubMed1987

Sensory innervation of the external and internal genitalia of the female rat.

Using a whole-nerve recording method, the genitalia of the female rat were found to receive afferent innervation as follows. Pelvic nerve: vagina, cervix, and perineal skin; hypogastric nerve: cervix and proximal three fifths of the uterus; pudendal nerve: skin of perineum, inner thigh, and clitoral sheath. It is probable that the pudendal and pelvic nerves are activated during copulation, and that all 3 nerves are activated during parturition.

Action Potentials↗

PubMed1987

Induction of maternal behavior in rats: effects of pseudopregnancy termination and placenta-smeared pups.

The onset of maternal behavior in Long-Evans rats was examined after pseudopregnancy (PsP) termination, both with and without exogenous estrogen administration, and in response to either clean or placenta-smeared stimulus pups. Natural (spontaneous) PsP termination was as effective in hastening the onset of maternal behavior as ovariectomy plus estrogen injection. If clean foster pups were presented as soon as pseudopregnancy terminated (first proestrus or cornified smear), maternal behavior was exhibited within 2 days; placenta-smeared foster pups presented at the same time elicited maternal behavior within 2 hr. The combination of initiating maternal-behavior testing immediately after the natural termination of pseudopregnancy and proffering placenta-smeared pups apparently simulates the hormonal milieu as well as the environmental cues present at parturition, noninvasively, producing optimal conditions for the rapid induction of maternal behavior.

Animals↗

PubMed1986

Ingestion of amniotic fluid enhances 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 whether AF ingestion, too, enhances analgesia; if so, whether the effect requires ingestion of, or merely exposure to, AF; whether the effect can be produced by AF delivered directly to the stomach by tube; and 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 rats that ingested AF after receiving a morphine injection showed significantly more analgesia than did rats that ingested a control substance; AF ingestion, alone, did not produce analgesia; ingestion of AF, rather than just smelling and seeing it, was necessary to produce analgesia enhancement; AF produced enhancement when oropharyngeal factors were eliminated by delivering it through an orogastric tube; and treatment of the rats with naltrexone blocked the enhancement of morphine-induced analgesia that results from AF ingestion.

Amniotic Fluid↗

PubMed1986

Effects of hypothalamic knife cuts and experience on maternal behavior in the rat.

Recent investigations suggest that the disruption of placentophagia, pup-directed maternal behavior, and nestbuilding seen after lesions of the medial preoptic area (MPO) or the lateral hypothalamus may be due to the interruption at different points of a single longitudinal neural system mediating these behaviors. To test this, we compared the effects of knife cuts on the lateral border of the MPO, and of the posterior medial forebrain bundle (MFB), with asymmetrical cuts combining a unilateral MPO cut with a contralateral MFB cut. We observed placentophagia, nestbuilding, and pup-directed maternal behaviors at, and after, parturition in both primiparous and biparous rats. In primiparae, MPO cuts (a) disrupted placentophagia, (b) delayed the onset of crouching and pup-licking, and (c) eliminated retrieval and nestbuilding. MFB cuts (a) disrupted placentophagia, (b) delayed the onset of maternal behavior, and (c) eliminated nestbuilding. Asymmetrical cuts (a) disrupted placentophagia, and (b) delayed the onset of maternal behavior. In biparous rats, MPO cuts eliminated nestbuilding and retrieval. MFB cuts (a) disrupted placentophagia, and (b) eliminated nestbuilding. Asymmetrical cuts (a) delayed nestbuilding. These results suggest the involvement of a longitudinal neural system in the production of immediate pup-directed maternal behavior, placentophagia, and nestbuilding in parturient primiparae, but which is not critical for the eventual display of maternal behavior and nestbuilding in maternally naive rats, nor for the immediate onset of placentophagia and maternal behavior in maternally experienced rats.

Animals↗

PubMed1986

Placenta ingestion enhances analgesia produced by vaginal/cervical 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.

Amniotic Fluid↗

PubMed1985

Placenta ingestion enhances opiate analgesia in rats.

Analgesia, produced by either a morphine injection or footshock, was monitored (using a tail-flick test) in nonpregnant female rats. Analgesia was induced within minutes of having the rats eat one of several substances. When the substance eaten was rat placenta, both the morphine- and shock-induced types of analgesia were significantly greater than in controls that ingested other substances (or nothing). When footshock (hind-paw) was administered in conjunction with the opiate antagonist naltrexone, the analgesia produced was attenuated but detectable; in this case, placenta ingestion did not enhance the analgesia, suggesting that the effect of placenta is specific to opiate-mediated analgesia. Placenta ingestion, in the absence of an analgesia-producing manipulation, did not elevate pain threshold. It is possible that this enhancement of analgesia is one of the principal benefits to mammalian mothers of ingesting the placenta and birth fluids (placentophagia) at delivery.

Analgesia↗