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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

Some comparisons among the calming and pain-relieving effects of sucrose, glucose, fructose and lactose in infant rats.

Ultrasonic vocalizations were recorded from 10-day-old albino rats while they were isolated from their dam and siblings. Each rat received a 1.0% BW intra-oral infusion of sucrose, fructose, glucose or lactose at a concentration range of 0.22-0.66 M for 3 min and their vocalizations were determined during the infusion and for an additional 7 min. Sucrose, fructose and glucose all significantly reduced vocalizations to about 50% of baseline levels, whereas lactose, the milk sugar, was ineffective. Moreover, the dose-response function was flat for the three effective sugars. In a second experiment, the effects of these sugars on heat escape latency were measured. Sucrose, fructose and glucose each elevated the latency with which infant rats removed a paw from a 48 degrees C surface; lactose did not. These findings of lactose ineffectiveness and the flat dose-response function for the other three sugars exactly parallel those obtained for human newborns. Their implications are discussed.

Analgesics

Behavioral and physiological consequences of suckling in rat and human newborns.

Suckling, in addition to yielding milk, water and calories, exerts profound behavioral effects on newborn rats and humans. In particular, suckling induces feelings of calm, reduces heart rate and metabolic rate, causes infants to bring their hands to their mouths and elevates the pain threshold. These changes are mediated by opioid and non-opioid systems, each having its own separate behavioral and neurological characteristics. The implications of suckling-induced changes for long-term motivational and cognitive change are discussed.

Adaptation, Psychological

A new look at some old mechanisms in human newborns: taste and tactile determinants of state, affect, and action.

Three studies of normal human newborns and of newborns of methadone-maintained mothers evaluated how orotactile (pacifier) and orogustatory (sucrose) stimulation, alone and in combination, affected crying behavior, heart rate, gross motor activity, eye opening, and hand-mouth coordination. For each measure of infant state, pacifier and sucrose stimulation each caused significant changes that followed very different time courses. Orotactile (pacifier) stimulation precipitated immediate changes in all behaviors, and, when the pacifier was removed, all behaviors soon reverted to baseline levels. The changes precipitated by orogustatory (sucrose) stimulation were more gradual but extended well beyond the end of sucrose administration. Although both pacifier and sucrose influences are mediated orally as opposed to in the stomach or intestine, the effects involve different brain pathways. The fact that infants born to methadone-maintained mothers did not change their behaviors during or after sucrose administration but that their reactions to pacifier stimulation could not be distinguished from those of normal infants suggests that reactions to sucrose are mediated centrally by endogenous opioids while those to the pacifier work through other central mechanisms. These findings with human newborns are consonant with those of many animal studies that have also shown rapid onset and rapid offset for contact- and suckling-induced behavioral changes, slower onset and slower offset for changes induced by taste, and opioid mediation of changes induced by the taste of sucrose. Orogustatory and orotactile influences on affect, action, and cardiovascular function are discussed from the perspectives of energetics and growth, central determinants of state, motivation, and learning during the newborn period.

Affect

The development of morphine-induced antinociception in neonatal rats: a comparison of forepaw, hindpaw, and tail retraction from a thermal stimulus.

Two parallel experiments in rats 2-21 days of age investigated the onset and characteristics of morphine-induced antinociception. One measure of reactivity to pain, limb retraction from a hotplate, was utilized for three different limbs (forepaw, hindpaw, and tail) to chart the development of opioid sensitivity. Morphine-induced antinociception, even in 2-day-old rats, was obtained for all limbs, in a dose-related fashion, and reached peak sensitivity at 6-7 days of age. Naltrexone did not affect limb retraction latencies in nonmorphine treated rats at any age. These studies demonstrate early antinociception to low doses of an opiate and establish that the pain system, like positive reinforcement systems, is opiate sensitive.

Analgesics

Endogenous cholecystokinin reduces vocalization in isolated 10-day-old rats.

Devazepide, the cholecystokinin (CCK) A receptor blocker, markedly and specifically affected the behavior of 10-day-old rats isolated from their mother and siblings. Whereas intraoral infusions of milk or fat, which cause CCK release, calmed infants, that is, reduced levels of ultrasonic vocalization, devazepide fully blocked this reduction. Devazepide did not affect calming caused by sucrose infusions, which do not release CCK. Moreover, devazepide did not reduce the elevated pain limen caused by milk or fat infusions. These data parallel earlier findings obtained with administration of exogenous CCK and implicate endogenous CCK in the maintenance of infant steady state and calm. The possibility that CCK contributes to the normal development of mother-infant affectional systems is discussed.

Animals

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