Feb. 17, 2005 BUFFALO, N.Y. -- A behavioral neuroscientist at the University at Buffalo holds that the ingestion of afterbirth by a mother, a feature of pregnancy in nearly all non-human mammals, not only relieves postpartum pain, but optimizes the onset of maternal behavior by mediating the activity of specific opioid activity circuits in the brain.
Mark Kristal, Ph.D., professor of psychology at UB and director the graduate program in behavioral neuroscience, has received a two-year $200,000 grant from the National Science Foundation, to test his hypothesis.
In 1986 Kristal discovered an opioid-enhancing molecule he called the Placental Opioid-Enhancing Factor or POEF.
His discovery led to a series of studies that shed light on the way in which POEF modulates how opioids inhibit nociceptive processing in the nervous system -- processing in specific areas of the brain that recognize certain kinds of pain.
Kristal says this research may lead to novel ways of treating addiction in humans by manipulating the effectiveness of the opiates we produce in our own bodies. It also may enable physicians to obtain current levels of pain relief, he says, "by administering much, much, much smaller amounts of opioid analgesics."
POEF is found in amniotic fluid and afterbirth. The new study, whose subjects will be mice, will test the hypothesis that it not only modulates pain, but operates on two specific brain centers to influence the subsequent emergence of maternal behavior.
"We think that endogenous opioid activation in the central nervous system at the end of pregnancy and during delivery -- that is, activity produced within the mammal, not introduced from without -- has a complex effect on maternal behavior," Kristal says. "It is our contention that this activation not only suppresses pain during delivery, but is responsible as well for the emergence of caretaking behavior toward the young.
"This activation is best described by focusing on two sites in the brain where it takes place," he says.
"Increased opioid activity in the ventral tegmental area, a motivation area of the brain, facilitates the onset of maternal behavior. Increased opioid activity in the medial preoptic area, however, a reproductive-behavior area of the brain, disrupts maternal behavior," Kristal explains.
"What we will test here is the hypothesis that afterbirth, when ingested, modifies specific opioid-receptor systems in those two brain regions," he says.
"We think that, in particular, POEF optimizes the onset of maternal behavior by enhancing the facilitating effect of opioids in the ventral tegmental area and attenuating the disruptive effects of opioids in the medial preoptic area. It does this by modifying the different types of opioid receptors in different ways."
"Humans don't eat afterbirth, of course," says Kristal. "In fact, there may be an adaptation in humans that mitigates against ingestion. We don't know. The introduction of POEF to human mothers after delivery to influence maternal behavior cannot be addressed at this point.
"Parturition in mammals occurs in the context of sensory, neurochemical and endocrinologoical factors orchestrated and timed so that maternal behavior and the object of this behavior, the newborn, 'emerge' almost simultaneously," Kristal says.
"In most species of mammals, these changes likely are initiated by sensory events arising in the distended reproductive tract and abdominal musculature and are modified by several things, including endocrine levels during delivery and the ingestion of substances by the mother in amniotic fluid and afterbirth," he says.
"Our goal here is to determine exactly how those substances, including POEF, interact with opioid activation areas in the brain and to describe the results of that interaction in non-human mammals."
Kristal is the former dean of the Faculty of Social Sciences at UB. In addition to his basic research into opioid and hormonal mechanisms, he studies the psychobiology of motivated behaviors.
His research regularly is published in such journals as Brain Research; Pharmacology, Biochemistry & Behavior, Synapse, Physiology & Behavior and Comparative Medicine.
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