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Biomedical subjects

E M Blass

Publications and source records attributed to E M Blass.

At least 19 recordsLinked to original sources

Mother as shield: differential effects of contact and nursing on pain responsivity in infant rats--evidence for nonopioid mediation.

To determine how rat mothers protect their pups against pain, we applied focal heat (34-51 degrees C) to the ear or shoulder of 10-day-old rats that were isolated, in contact among themselves or with their mother, suckling nonnutritively, or in the hyperextension position normally caused by milk letdown. Relative to isolated rats, contact doubled withdrawal latencies from heat (43 or 45 degrees C) applied to the ear. Suckling quadrupled heat-escape latencies. During hyperextension, rats essentially did not escape from thermal stimulation of up to 48 degrees C. Protection provided by maternal contact, especially suckling, was not mediated by either mu or kappa opioid receptors: neither systemic injections of naltrexone nor norbinaltorphimine reduced heat-escape latencies. Morphine (0.125 and 0.250 mg/kg) added to the effects of contact but multiplied the effects of suckling to produce heat-escape latencies that were upward of 2 min.

Animals

Pain-reducing properties of sucrose in human newborns.

To assess the characteristics of sucrose as a pain-reducing substance, crying in 72 newborn humans during and after blood collection via heel prick was determined. In the first study infants drank 2 ml of water or 2 ml of a 0.17-0.34- or 0.51-M sucrose solution 1 min prior to blood collection. In the second experiment, a delay of 30, 60, 90, 120 or 240 s was imposed between sucrose intake and the initiation of blood collection. The dose-response function for concentration was flat. The most effective time delay was 120 s. The effectiveness of the 2-min interval accords with previous findings of endogenous opioid release caused by sucrose taste. The flat dose-response function extends findings in rats and humans that the calming and pain-reducing effects of sucrose are not influenced by either concentration or volume, suggesting that the transduction from gustatory afferent to opioid-mediated efferent is of an on-off nature and not graded.

Analgesics, Non-Narcotic

Opioid mediation of odor preferences induced by sugar and fat in 6-day-old rats.

Intraoral infusions of sucrose, fat or polycose reduce ultrasonic vocalizations during isolation, and increase pain threshold in infant rats. These effects are naltrexone reversible. The present study determined whether these substances, when paired with an odor, caused a change in preference for that odor. In 6-day-old rats, pairing orange odor with intraoral infusions of sucrose or corn oil, but not polycose, water, mineral oil or 0.01% quinine hydrochloride, caused a substantial increase in preference for orange. Preference formation was blocked by systemic injection of naltrexone (0.25 mg/kg) prior to pairing orange with either sucrose or corn oil. Moreover, preference expression was prevented by naltrexone injection prior to testing. Thus certain substances thought to reduce stress in infant rats via endogenous opioid release can also cause preference for substances that predict their occurrence. Preference formation depends upon the availability of endogenous opioids. Preference expression reflects the conditioned stimulus causing opioid release.

Animals

Milk-induced, opioid-mediated antinociception in rats at the time of cesarean delivery.

Four experiments were conducted in rats within 2 hr of cesarean delivery to assess antinociception at birth and its possible opioid bases. Morphine antinociception was established in a dose-dependent fashion (0.0625-5.0 mg/kg bw). Analgesia was naloxone (1.0 mg/kg) reversible. In succeeding experiments, antinociception equivalent to that produced by 0.0625-0.125 mg/kg morphine injections was induced by a single 20-microliters bolus of milk (commercial half-and-half) that was delivered over 1-2 s to the middle of the tongue. This, too, was naloxone reversible. Milk-induced antinociception was maintained for at least 4 min. Finally, baseline latencies were progressively reduced during the first 2 hr after delivery to levels (8-10 s) that are typically obtained in older (10-day-old) rats. This decline was not opioid mediated because it was not affected by naloxone. Thus, at birth, delivering milk to the mouth in physiological volumes can exert opioid-mediated antinociceptive effects in rats born by cesarean delivery that had never suckled or experienced any other form of maternal contact.

Animals

Sucrose as an analgesic for newborn infants.

The effectiveness of sucrose as an analgesic agent for newborn infants was assessed during two standard painful hospital procedures: blood collection via heel lance and circumcision. Infants who drank 2 mL of a 12% sucrose solution prior to blood collection cried 50% less during the blood collection procedure than did control infants who had received 2 mL of sterile water. Crying of infants who ingested sucrose returned to baseline levels within 30 to 60 seconds after blood collection whereas control infants required 2.5 to 3.0 minutes to return to baseline. Like findings were obtained for infants who received sucrose on a pacifier prior to and during circumcision. Specifically, control infants who underwent a standard circumcision procedure without intervention cried 67% of the time. A water-moistened pacifier reduced crying to 49% (P less than .01). Crying was reduced further to 31% (P less than .05) by providing infants with a sucrose-flavored pacifier to suck. These findings, which parallel results obtained in studies of pain in infant rats, provide a potent yet simple, benign intervention to help alleviate stress and pain routinely experienced by human infants.

Administration, Oral

Cholecystokinin conditioning in rats: ontogenetic determinants.

Low doses (0.12-2.0 micrograms/kg) of cholecystokinin octapeptide (CCK), administered intraperitoneally, support the formation of conditioned odor preference in neonatal and weanling rats. Exposure to a novel odor was paired with CCK injection, and the rats' olfactory choices were assessed 24 hr later. Rats at 5, 11, and 22 days of age preferred the odor previously associated with CCK, compared with vehicle-injected littermates. In contrast, CCK failed to support olfactory conditioning in 28-day-old rats, whether they were (a) weaned and independently housed, (b) residing with the dam and suckling, or (c) fed only milk. Adult rats also did not establish an odor preference with CCK as the unconditioned stimulus. Thus, CCK's changing impact from positive to neutral probably occurs during the rats' 4th postnatal week and may be related to maturational changes occurring during the final stages of weaning.

Animals

Separation of opioid from nonopioid mediation of affect in neonatal rats: nonopioid mechanisms mediate maternal contact influences.

A causal distinction is established in infant Norway rats between opioid- and nonopioid-mediated determinants of behavior. Contact influences are shown to be mediated by nonopioid pathways, whereas gustatory influences are shown to be opioid mediated. Specifically, naltrexone (0.5 and 1.0 mg/kg) did not at all diminish quieting exerted by contact with an anesthetized dam but completely reversed the quieting effects of morphine in isolated rats. Naloxone (5 mg/kg) did not affect the latencies with which nondeprived or 8-hr deprived rats 9, 12, 15, and 18 days of age attached to the nipples of anesthetized dams, nor did naloxone (5 and 10 mg/kg) cause any systematic change in nipple attachment in 10- and 18-day-old rats that had been deprived of their dam for either 0, 8, or 24 hr. In a 3rd experiment, naloxone (5 mg/kg) did not significantly reduce milk intake by 9-, 12-, 15-, or 18-day-old rats from the nipple when milk letdown was induced by oxytocin. Moreover, naloxone (5 and 10 mg/kg) did not reduce milk intake in Day-10 rats that, while suckling, received milk via a cannula placed in the posterior portion of the tongue at the level of the intermolar eminence or in rats that obtained milk directly from their awake mother. In contrast, milk intake was significantly reduced by naltrexone (0.25-1.0 mg/kg) in Day-10 rats that obtained milk (a) by licking it off a saturated substrate or (b) through an indwelling cannula located in the anterior portion of the lower jaw. (Milk delivered at this placement is thought to engage feeding systems by its taste and texture.) In a final set of experiments in Day-10 rats, intake of milk delivered via anterior jaw cannulae was reduced by naloxone (5 and 10 mg/kg) in rats that were either isolated, in contact with an anesthetized dam, or attached to her nipples. On the basis of resistance to naloxone and naltrexone administration, these experiments demonstrate that behavioral influences of the tactile (and possibly olfactory) qualities of the mother are not mediated by opioid systems. Implications for understanding the means through which mothers can influence their young and the infantile mediators of these maternal influences are discussed.

Affect

Conditioned opioid release in ten-day-old rats.

Ten-day-old rats, for whom an orange scent predicted morphine injections at 5 days of age, exhibited a marked preference for orange that was fully naltrexone reversible. Moreover, such rats, when smelling orange during a heat-escape task, exhibited a higher pain threshold than control rats. Together, these findings suggest that the orange odor in conditioned rats caused a release of endogenous opioids that both sustained choice behavior and modulated pain systems.

Animals

Opioidlike effects of intraoral infusions of corn oil and polycose on stress reactions in 10-day-old rats.

The effects of intraoral infusions of corn oil and the polysaccharide Polycose on behavioral reactions to pain and to social isolation were studied in 10-day-old albino rat pups. Both substances significantly increased paw-lift latencies (a measure of pain response) and reduced the number of ultrasonic vocalizations (a measure of isolation distress). Moreover, elevated pain thresholds were normalized by naltrexone (0.25 mg/kg) pretreatment, and the quieting of vocalizations was abolished by pretreatment. These findings indicate an interaction between ingestion, pain, and distress systems in neonatal rats and suggest that fats and polysaccharides influence these systems via endogenous opioids.

Animals

Stress-reducing effects of ingesting milk, sugars, and fats. A developmental perspective.

A developmental approach to the study of feeding is proposed that considers social complexity and its biological mediation as core determinants of later ingestive patterns. Evidence is presented for opioid-mediated influences of milk and its major constituents and for nonopioid-mediated channels for contact comfort. Consideration of these factors might help us better understand some of the determinants of human feeding disorders such as bulimia and anorexia nervosa.

Animals

Sensory determinants of nipple-attachment behavior in 2-4-day-old kittens.

Fourteen kittens, 2-4 days of age, were studied on their anesthetized dams for nipple attachment behavior. In agreement with a previous report (Larson, M. A., & Stein, B. E., 1984, Dev. Psychobiol., 17: 423-436) we find that olfaction contributed rather little to nipple attachment in kittens. The major determinants appear to be tactile, centering in the mouth and trigeminal projection field. The behavior of kittens with temporary oral and/or trigeminal deafferentation is described in detail to provide some understanding of the contribution of each of those areas to nipple attachment in kittens.

Animals

Milk-induced analgesia and comforting in 10-day-old rats: opioid mediation.

The effects of slow intraoral milk infusions on the opioid-mediated behaviors of ultrasonic vocalizations and paw removal from a hot plate (48-49 degrees C) were evaluated in 10-day-old rats. Milk reduced distress vocalization by circa 30% while increasing paw lift latencies by about 60%. Alterations in both behaviors were fully reversed by naltrexone (0.5 mg/kg) pretreatments. These data demonstrate the calming and analgesic effects of milk. Implications for a possible role of opioid peptides in mother-young relationships are discussed.

Acoustic Stimulation

Behavioral evidence for cholecystokinin-opiate interactions in neonatal rats.

In adult mammals, cholecystokinin (CCK)-opiate interactions are complex and task dependent. Specifically, CCK antagonizes opiate effects in some cases, yet acts similarly to opiate agonists in others. The present study used behavioral measures to determine how CCK interacts with opiates in neonatal rats. CCK, at doses of 1 microgram/kg and higher, markedly reduced isolation-induced distress vocalization in rat pups. Moreover, CCK selectively prevented naltrexone antagonism of opiate-mediated reduction in distress vocalization in 3- and 11-day-old rats. Yet CCK did not affect opiate-induced analgesia, as measured by the hot-plate paw-lift response. Thus CCK either did not interact with opiates or did so agonistically, with the same (low) dose range, and within subjects. These findings suggest independence of stress and pain systems in neonatal rats and demonstrate a functional interaction between CCK and opioid systems.

Animals

Development of postglucoprivic insulin-induced suckling and feeding in rats.

Increased food or milk intake in response to insulin-induced hypoglycemia cannot be demonstrated in the rat until pups reach weaning age. However, when food and suckling are withheld from insulin-treated 5- to 25-day-old rats until their altered blood glucose levels return to normal, their rate of milk intake via suckling from their anesthetized dam is increased over saline-treated control pups. This postglucoprivic action of insulin could not be demonstrated in rats consuming wet mash until pups reached 25-30 days of age. Nonnutritive oral stimulation from dry suckling during the glucoprivic episode is sufficient to disrupt postglucoprivic suckling in 20-day-old rats. In contrast consuming a small quantity of wet mash became an effective inhibitor of postglucoprivic suckling only when pups reached 25 days of age. These data demonstrate the existence of an insulin-sensitive neural system for suckling and feeding in infant rats and point to the involvement of multiple and changing oral factors during development in insulin-induced postglucoprivic feeding.

Animals

Infantile experience with suckling odors determines adult sexual behavior in male rats.

Because infant rats learn about odors that elicit suckling, and because certain chemosensory cues that help elicit mating behavior in adults are similar to those that elicit suckling, an experiment was undertaken to assess the influence of suckling-associated odors experienced during infancy on adult sexual behavior. Rat pups lived with and suckled dams whose nipple and vaginal odors were altered with citral, a lemon scent. The rats were weaned and never exposed again, until testing, to citral or females. At about 100 days of age, the males were paired in mating tests with a normal sexually receptive female or with a sexually receptive female that had been treated perivaginally with citral immediately before testing. The males ejaculated readily when paired with citral-treated females but were slow to achieve ejaculation when paired with normal females. These findings implicate an infantile experience as a determinant of adult sexual behavior in a mammal.

Animal Population Groups

Opioid-mediation of separation distress in 10-day-old rats: reversal of stress with maternal stimuli.

A relationship between distress vocalizations, response to nociception and their opioid mediation in 10-day-old maternally isolated rat pups was established. The comforting effects of several classes of biological stimuli were examined. Short-term (5 min) isolation from mother, siblings and nest caused a significant analgesic response to heat (48 degrees C) relative to nonisolated siblings. Morphine administration markedly increased heat escape latencies and decreased distress vocalizations during isolation. Naltrexone, an opioid antagonist, had the opposite effect; escape latencies were halved and distress vocalizations doubled. Contact with an anesthetized female, dam or virgin, immediately reduced both analgesia and vocalizations. Home-bedding was only effective after 5 min exposure, whereas clean bedding did not reduce isolation-induced behaviors. These results are discussed in terms of infant learning and motivation under natural circumstances.

Animals

Central nervous system mediation of positive and negative reinforcement in neonatal albino rats.

Two classes of affective behaviors served as assays for central opioid mediation of affect during development. On the positive side, we found that 5-day-old rats came to prefer a novel odor that predicted the delivery of morphine intracerebroventricularly, thereby replicating previous findings with peripheral morphine. Moreover, central naltrexone blocked the odor preference formation associated with peripheral morphine. In examining responses to pain and stress, we found that central morphine decreased sensitivity to pain, as measured by paw withdrawal to heat and decreased ultrasonic vocalizations during isolation. Conversely, naltrexone delivered intracerebrally increased sensitivity to a painful stimulus and markedly increased distress vocalizations relative to untreated isolates. Thus, the present results imply that central opioid systems are functional behaviorally in neonatal rats mediating affective responses.

Affect