Fetal experience with milk or an artificial nipple alters appetitive and aversive responses to perioral cutaneous stimuli

Fetal rats exhibit oral grasping of an artificial nipple. The authors examined interactive effects of sensory stimuli normally encountered in the suckling environment on subsequent responses to the nipple. Embryonic Day 20 rat fetuses received an infusion of milk, lemon, or saline through a hollow artificial nipple or an intraoral cannula (producing no nipple stimulation). One minute after sensory pretreatment, behavioral responses of fetuses to an artificial nipple were recorded on videotape for frame-by-frame analysis. Preexposure to the artificial nipple decreased the number of oral grasps and facial wipes directed toward the artificial nipple but increased the duration of grasp responses. Milk uniformly reduced fetal responsiveness to the nipple. Furthermore, the artificial nipple enhanced fetal responses to perioral cutaneous stimulation, whereas milk suppressed perioral responsiveness. These data suggest that the perinatal rat's 1st experience with milk or the nipple can alter subsequent responses to suckling stimuli.     

Behavior of rat fetuses following chemical or tactile stimulation.

The behavior of fetal rats was examined on Day 19 of gestation with procedures that enabled chemical stimulation and direct observation of fetuses. Rat fetuses are sensitive to both tactile stroking and intraoral infusion of chemical solutions, but the pattern and amount of activity depend upon the modality of stimulation. Fetal responsiveness is affected by prior experience with chemical stimuli. Repeated exposure within a 10-min period results in a waning of response, and repeated exposure across a delay of 48 hr results in a different pattern of response than is seen to a novel stimulus. Reexposure to a stimulus experienced earlier in gestation also alters fetal responsiveness to other forms of tactile and chemical stimulation. These findings indicate that the rat exhibits olfactory function in utero and suggest central processing of sensory information, including evidence of habituation, a fetal orienting reflex to novel stimuli, and the existence of prenatal behavioral states associated with different patterns of response. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Norepinephrine and posttraining memory consolidation in neonatal rats.

Wistar rat pups, aged Postnatal Day 5, were trained in an olfactory associative learning task with citral odor as the conditioned stimulus (CS) and intraoral infusions of milk as the unconditioned stimulus (US). Following a 30-min training session, pups were injected with either the norephinephrine 13-receptor antagonist propranolol or the β-receptor agonist isoproterenol. Pups were tested 24 hr later for an acquired relative odor preference for the CS. Propranolol injected immediately following training impaired memory for the CS in a dose-dependent manner. This posttraining effect lasted less than 4 hr. Isoproterenol injected immediately after training also impaired memory performance, even at very low doses. These results suggest that posttraining levels of norepinephrine play a critical role in memory consolidation in the newborn, with elevations or decrements in noradrenergic activity resulting in impaired memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cryptopsychobiology: The appearance, disappearance, and reappearance of a species-typical action pattern during early development.

Late in gestation, intraoral infusion of lemon elicits a facial wiping response from rat fetuses. This facial wiping response is isomorphic with that of older pups and adult rats exposed to aversive oral stimulation. Most studies of the postnatal development of aversive responses have demonstrated that facial wiping does not appear in the repertoire of rat pups until the second postnatal week. In certain test situations, however, wiping can be elicited from neonatal rats. This fact suggests that the expression of facial wiping by neonates is constrained or facilitated by the environmental conditions present at the time of testing. In this report, a series of seven experiments is described that document the wiping response of rat fetuses and pups in age-typical environments, and an environmental constraint hypothesis is examined. Examination of the ontogeny of facial wiping in this manner highlights issues that should be addressed in studies of behavioral continuity between the prenatal and the postnatal periods. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Classical conditioning of opioid activity in the fetal rat.

Milk promotes activity in the kappa opioid system of the rat fetus that reduces responsiveness to cutaneous stimulation. In this study, fetuses on Gestational Day 20 were presented with an artificial nipple (conditioned stimulus [CS]) paired with an intraoral infusion of milk (unconditioned stimulus [UCS]). One paired presentation of the CS and UCS reduced fetal responsiveness after reexposure to the CS. Selective antagonism of opioid receptors after conditioning indicated that reduced responsiveness was due to mu opioid activity. Mu and kappa opioid activity was evident after 3 paired presentations of CS and UCS and reexposure to milk. Kappa opioid activity during conditioning was necessary for mu involvement after reexposure to the CS or UCS. These experiments, which were conducted with fetal Ss that lacked suckling experience, suggest that neurochemical systems engaged during suckling may change rapidly after the newborn's initial experiences at the nipple. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Habituation to chemosensory stimuli in the rat fetus: Effects of endogenous kappa opioid activity.

On Day 21 of gestation, rat fetuses respond to chemosensory stimuli by expressing stereotypic facial wiping behavior. A series of 4 experiments was conducted to investigate (1) the influence of morphine on fetal responsiveness to a single chemosensory infusion, (2) the effect of naloxone blockade of endogenous opioid activity on diminished fetal responsiveness over a series of chemosensory infusions, (3) the effect of endogenous opioids on the recovery of fetal responsiveness to infusion after various dishabituation procedures, and (4) the influence of selective mu and kappa opioid receptor antagonists on fetal habituation. These experiments confirm that fetuses habituate after a brief series of chemosensory infusions and that dishabituation promoted by presentation of a novel stimulus is facilitated by pharmacological blockade of kappa opioid receptors. Endogenous activity in the kappa opioid system may be functional in modulating the sensory environment around the time of birth. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rapid and robust olfactory conditioning with milk before suckling experience: Promotion of nipple attachment in the newborn rat.

An olfactory conditioning paradigm tested the hypothesis that newborn rats are able to learn about events associated with their first experience with milk as early as 3–5 hr after birth. Exposure to lemon odor (conditioned stimulus, [CS]) paired with intraoral milk infusions (unconditioned stimulus, [US]) resulted in strong conditioning: In the presence of the CS, sustained attachment occurred to an empty nipple as if it provided milk, whereas pups in control conditions showed little attachment. A single CS–US pairing was sufficient for strong conditioning, which was evident with a trace interval as long as 60 s. Conditioning was robust enough to promote attachment to a nipple providing saline, which is aversive to the newborn rat, and comparably strong conditioning occurred with sucrose or saccharin as the US. These findings suggest that olfactory conditioning has the potential to modify suckling behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ontogeny of the stretch response in the rat fetus: Kappa opioid involvement.

Previous studies have demonstrated that the kappa opioid system is functional and plays a role in mediating the stretch response of the rat fetus on Day 21 of gestation. In this study, a kappa opioid agonist (U50,488) was administered on Days 19, 20, or 21, and fetal behavior was recorded after infusion of either milk or saline. Activation of the kappa opioid system promoted stretching in response to saline on Days 20 and 21. Although fetuses on Day 19 did not stretch, videotape analysis indicated that kappa opioid manipulation promoted modest increases in rearlimb activity and changes in fetal body posture that typically occur antecedent to the stretch. These findings suggest that functional maturity of the kappa opioid system may be a limiting factor in the expression of the fetal stretch response. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The rat fetus in its environment: Behavioral adjustments to novel, familiar, aversive, and conditioned stimuli presented in utero.

128 Sprague-Dawley rat fetuses were exposed on Day 17 of gestation to a taste/odor stimulus (mint) injected into the amniotic fluid and/or LiCl injected into the peritoneum. Behavior of injected fetuses was directly observed on Day 19 of gestation following chemomyelotomy and laparotomy of the female and immersion of the uterus into a warm saline bath. With these procedures, a series of 4 experiments was conducted to assess the behavioral effects of (a) the mint taste/odor alone, (b) the LiCl alone, (c) the pairing of mint and LiCl on the day of conditioning, and (d) the reexposure to mint after an earlier pairing of mint and LiCl. Findings provide evidence that rat fetuses were capable of forming conditioned taste/odor aversions as early as Day 17 of gestation and, further, that rat fetuses were capable of expressing these learned aversions in utero. (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Behavioral responses of the chronically instrumented sheep fetus to chemosensory stimuli presented in utero.

Fetal sheep were surgically prepared on Days 113–114 of gestation with an array of chronic instruments for recording electromyographic data (EMG) in oral-facial, axial, and limb muscles and heart rate (FHR). Fetuses also were fitted with an intraoral catheter for infusion of chemosensory fluids (isotonic saline, quinine, colostrum, sucrose) onto the surface of the tongue. Individual subjects received chemosensory infusions on Days 134–137. Fetuses showed consistent oral responses to quinine and milk, but did not respond to isotonic saline or sucrose. Different patterns of motor responses suggested that fetuses discriminated among different concentrations of quinine. The expression of tachycardia to quinine and bradycardia to milk also suggested differential responding to chemosensory fluids that differ in hedonic qualities Detailed characterization of fetal responses to these stimuli in utero confirm the functionality of the gustatory system in the sheep fetus near term. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Olfactory aversive conditioning in the newborn (3-hr-old) rat impairs later suckling for water and milk.

An olfactory conditioning paradigm tested whether newborn rats can acquire a conditioned aversion to olfactory events associated with their first postnatal meal 3-5 hr after birth. Exposure to lemon odor (conditioned stimulus [CS]) paired with intraoral infusions of 0.1% quinine (unconditioned stimulus) resulted in explicit conditioning. Responsiveness to a surrogate nipple providing water in the presence of the CS was significantly lower than the 3 control conditions. The conditioning dramatically suppressed responsiveness to a surrogate nipple providing milk, which normally is expressed voraciously in terms of sustained nipple attachment and milk intake. These findings suggest that as early as 3-5 hr after birth newborn rats are capable of aversive conditioning to odors in the context of suckling behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Stimulus contingencies that permit classical conditioning of opioid activity in the rat fetus.

In a prenatal model of classical conditioning, rat fetuses received presentations of an artificial nipple (conditioned stimulus; CS) paired with milk (unconditioned stimulus). Infusion of milk promotes activity in the kappa opioid system of the fetus, but after 2, 3, or 6 pairings with the artificial nipple, milk evoked both kappa and mu opioid activity. The nipple CS has no effect on opioid activity, but after pairing with milk evoked a mu opioid response. Conditioned mu opioid activity was evident in 60% of subjects tested after I paired conditioning trial. Significantly more fetal subjects (90%) exhibited conditioned opioid activity if preexposed to the nipple twice before conditioning. CS preexposure altered behavior during the conditioning trial, with preexposed fetuses showing more pronounced responses to milk infusion. Exposure to familiar stimuli facilitates classical conditioning of physiological responses, including opioid activity, during the first suckling episode. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sleep: a prerequisite for reflex milk ejection in the rat

Electroencephalographic activity (EEG) was recorded from the frontal cortex of unanaesthetized and urethane-anaesthetized lactating rats and analysed in relation to the pattern of milk ejection evoked by the nursing pups. The EEG of the anaesthetized rat fluctuated without experimental intervention between three distinctive patterns defined as synchronized, desychronized, and stage III activity, whilst reflex milk ejection recurred at intervals of about 6 min (range 2- greater than 20 min) throughout the 1-4 h period the pups were left attached to the nipples. For greater than 10 s before and for up to 60 s after each milk ejection, as judged from recordings of intramammary pressure and pup behaviour, the EEG was invariably synchronized throughout. Conversely, milk ejection (n greater than 300) was never observed during long periods of desynchronized, or stage III EEG activity. The vigorous increase in the sucking of the pups at milk ejection failed to produce a desynchronization (arousal) of the EEG as observed with other forms of sensory stimulation. Indeed, the sucking of the pups appeared to produce a soporific change i, the maternal EEG for spontaneous periods of desynchronization were not observed in the 30-60 min following the initial attachment of the pups to the nipples. Similar EEG patterns were seen in the unanaesthetized rat, though arousal from the synchronized state was more easily produced, e.g., by weak auditory signals. Milk ejection, as judged from the behaviour of the pups, recurred at intervals of 2 min or more during each 20-80 min period of nursing. The rat appeared somnolent for most of the nursing period and the EEG was always synchronized for greater than 10 s before each milk ejection (n greater than 200), though her eyes usually remained open. Arousal and desynchronization of the EEG was invariably observed in association with the increased pup behaviour at milk ejection. From these observations and the knowledge that oxytocin release from the neurohypophysis occurs about 10 s before milk ejection, we conclude that a synchronized EEG pattite for the expression of the milk-ejection reflex in the rat.     

The ontogeny of feeding in rats: I. Ingestive and behavioral responses to oral infusions.

Reports on 3 experiments with Charles River rat pups. When milk infusions were made through oral cannulas in the front of their mouths, 1–20 day old Ss actively ingested the diet, and their intake was related to the length of deprivation. Ss decreased their ingestive responding after they had consumed large volumes of milk. In addition, 1-, 3-, and 6-day-old Ss, when 24-hr deprived, exhibited an intense behavioral activation in response to milk infusion. The behavioral activation appeared to be stimulated primarily by taste and the opportunity to swallow. Milk infusions did not produce activation in older Ss; their behavior was more exclusively ingestive and food directed. Results demonstrate that (a) from birth, rat pups are capable of an active form of ingestion, independent of normal suckling from the mother; (b) such ingestion is controlled by physiological factors; (c) food has arousing properties in young animals; and (d) as pups grow older, their ingestive responding is refined from a generalized and nondirected activation to specific and directed feeding responses. (57 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prenatal binge ethanol exposure on gestation days 19–20, but not on days 17–18, increases postnatal ethanol acceptance in rats.

Previous research shows that prenatal binge ethanol exposure during gestation days (GD) 17 to 20 of the rat, increases postnatal ethanol intake and enhances ethanol's palatability, both effects being mediated by the opioid system. The amniotic fluid of the last period of gestation (GD 20) of the rat has been found to activate the opioid system and to induce conditioned preference in fetal and neonatal rats. We aimed to investigate whether enhanced acceptance for ethanol is observed when rat fetuses are exposed to it either on GD 17–18 or on GD 19–20. The results show that 14-day old pups whose mothers received ethanol on GD 19–20 consumed more ethanol and found ethanol more palatable when compared to pups exposed to ethanol on GD 17–18, or to pups experiencing ethanol and naloxone on GD 19–20. The augmented ethanol intake was observed as well after weaning (PD 26–27). These data indicate that exposure to ethanol on GD 19–20, but not before, triggers appetitive learning related to ethanol's flavor. This prenatally acquired memory is retained for at least 4 weeks and can be detected postnatally as enhanced palatability of ethanol's flavor as well as increased intake of ethanol. This increased liking of ethanol is mediated by the opioid system, although it cannot be clearly determined whether the prenatal activation of the opioid system is induced by the action of ethanol or by the activity of amniotic fluid components at that gestational age. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Behavioral effects of centrally administered arginine vasopressin in the rat fetus.

Arginine–8 vasopressin (AVP) was administered to rat fetuses on Embryonic Day 20 via intracisternal (IC), intrahemispheric (IH), or intrathecal (IT) injection. The IC administration of AVP promoted a 4-fold increase in motor activity, including the uncommon patterns of mouthing, licking, and facial wiping. The IH injection of AVP had little effect on fetal behavior, but IT injection resulted in pronounced increases in fetal activity, including mouthing, licking, and wiping. The IT administration of a V? antagonist blocked AVP effects, whereas IH injection potentiated AVP-induced changes in fetal behavior. The IC blockade of V? receptors suppressed facial wiping to a chemosensory fluid (lemon) and reduced oral grasping of an artificial nipple, whereas IH injection of the V? antagonist promoted facial wiping responses and increased grasping of the nipple. These data suggest that AVP may play a role in the development of responsiveness to stimuli encountered in the context of suckling. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dissociation of autonomic and behavioral components of conditioned fear during development in the rat.

Examined classical conditioning of heart rate (HR) in unrestrained preweanling and weanling Sprague-Dawley rats (aged 16, 19, 21, 25, and 28 days old), with tone and light as the conditioned stimulus/stimuli (CS) and electric shock as the unconditioned stimulus/stimuli (UCS). The conditioned cardiac response was a sustained deceleration in HR that did not emerge until Day 21 for the tone CS and until Day 28 for the light CS. In contrast, when suppression of a behavioral response (running in a straight alley for dry suckling as reward) was used as the index of conditioning, the suppressive effects of the CS were evident around Day 16 for the tone and around Day 19 for the light. Findings indicate that during ontogenesis (a) the behavioral and autonomic responses to the same CS do not develop at the same pace; (b) the emergence of conditioned responses (CRs) to tone and light stimuli parallel the sequential order in which the relevant sensory modalities achieve maturity (first audition, next vision); and (c) there is no clear-cut interdependence between development of the HR orienting response and conditionability of HR because unconditioned cardiac deceleration to both auditory and visual stimuli first appears about Day 16 in the developing rat, well before conditioned HR responses can be established to either stimulus. (34 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Brain transections selectively alter ingestion and behavioral activation in neonatal rats.

Food-deprived neonatal rats actively ingest milk that is infused into their mouths through intraoral cannulas. This ingestion is accompanied by behavioral activation. The involvement of various brain regions in ingestion and activation was examined in 2-day-old Charles River pups by making transections along the neuraxis from the olfactory bulbs to the anterior pons. Following a 24-hr deprivation period, a series of oral milk infusions was given, and milk intake and activity were measured. Intake was severely reduced only in Ss with diencephalic transections. Cuts in front of or behind the diencephalon resulted in normal or slightly decreased intake. In contrast, activity tended to decline as the level of the transection became more caudal. Thus ingestion and its accompanying behavioral activation could be separated neuroanatomically. These results suggest that 2 brain mechanisms are involved in the ingestive response of the infant rat, one in the diencephalon and another caudal to the mesencephalon. However, behavioral activation appears less discretely organized, involving most of the neuraxis. (28 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Maternal contributions to sensory experience in the fetal and newborn rat (Rattus norvegicus).

Using videographic analyses, maternal contributions to the sensory environment of the perinatal rat were identified and quantified by analyzing, from the offspring's perspective, the dam's activities during gestation, labor, and delivery. The observations indicate that pregnant females remain highly active during the final week of gestation, as compared with nonpregnant control animals. Exploratory movements, feeding, drinking, self-grooming, and other activities of the rat dam pitch, turn, accelerate, and expose fetuses to mechanical pressures. During parturition uterine contractions and maternal licking and handling provide vigorous tactile and vestibular stimuli to pups. Newly born pups are exposed to intense thermal stimulation, cooling rapidly to the temperature of the postnatal environment. Results suggest that fetal and newborn rats are exposed during development to a broad range of maternally produced stimuli. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Development and habituation of the heart rate orienting response to auditory and visual stimuli in the rat.

Studied development and habituation of responsivity to sound and visual stimuli in 120 8–19 day old Sprague-Dawley pups by using a change in heart rate (HR) as the indicant response (Exp I). A change in HR to sound (white noise) first occurred around 14–25 days of age and was acceleratory in nature. Within 3 days, the direction of the HR response shifted to bradycardia. The HR response to light was also characterized by tachycardia in young pups (14 days), which shifted to bradycardia as the pups matured (16 days and older). In Exp II, the HR response of 15- and 19-day-old Ss was studied at 3 auditory stimulus intensities (60, 70, and 90 db, B scale). Stimulus intensity influenced the magnitude of the cardiac response in the 19-day-old pups. Data suggest that even weak sensory stimuli elicited a defensive reaction (HR acceleration) during the 1st few days that followed onset of function in each sensory system; later in development, the same stimulus elicited an orienting response (cardiac deceleration). (25 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)