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S R Robinson

Publications and source records attributed to S R Robinson.

At least 73 records · Page 4Linked to original sources

Fetal behavior and the endogenous opioid system: D1 dopamine receptor interactions with the kappa opioid system.

Opioid or dopaminergic drugs can alter the motor behavior of rat fetuses on day 21 of gestation (E21). This study was conducted to a) characterize the behavioral effects of specific opioid agonists in the fetus, b) determine the effects of selective blockade of opioid receptors, and c) characterize the interaction between the dopamine and kappa opioid systems. Neither morphine nor the mu agonist DAMGO produced effects on fetal motor activity, whereas the kappa agonist U50,488 resulted in a pronounced increase in motor behavior. The selective antagonists beta-funaltrexamine (mu) and nor-binaltorphimine (kappa) produced no behavioral effects when administered alone. The D1 antagonist SCH-23390 did not reverse the activational effects produced by U50,488, but the kappa antagonist nor-binaltorphimine successfully blocked the increases in fetal behavior produced by the D1 agonist SKF-38393. These results are consistent with the hypothesis that activation of the dopamine system promotes activity at kappa opioid receptors to bring about changes in fetal motor activity.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Mu and kappa opioid systems modulate responses to cutaneous perioral stimulation in the fetal rat.

The prenatal ontogeny of functional mu and kappa opioid systems was investigated in a series of four experiments conducted with rat fetuses on the last day of gestation (E21). Fetal motor activity and responsiveness to cutaneous stimulation were measured following administration of various opioid agonists, including morphine, DAMGO, U69,593, and U50,488. The effectiveness of selective mu (CTOP) and kappa (nor-binaltorphimine) antagonists to block the effects of opioid agonists, and the effects of combined administration of DAMGO and U69,593, also were assessed. These experiments provide evidence that both mu and kappa opioid systems are functional and are capable of modulating fetal behavior during the late prenatal period. The data also suggest that different subclasses of kappa receptors may mediate different aspects of fetal behavior. These findings suggest a role for endogenous opioids in regulating important aspects of perinatal behavior, including the development of suckling, maternal-infant interaction and early learning at the nipple.

Animals↗

Fetal behavior and the dopamine system: activity effects of D1 and D2 receptor manipulations.

Binding studies have indicated that D1 and D2 dopamine receptor subtypes are present in rats before birth, but it is not known whether these receptors are functional during the prenatal period. In the present study, day-21 rat fetuses were prepared for direct observation after pharmacological manipulation of D1 and/or D2 receptors. The D1 agonist SK&F38393 induced a marked increase in fetal activity (i.e., forelimb, rearlimb, and head movements) while the D2 agonist quinpirole produced a slight suppression in activity. Coadministration of both agonists resulted in low levels of fetal activity, suggesting an interaction between D1 and D2 receptors. Administration of the D2 antagonist sulpiride resulted in little change in fetal behavior but was effective in blocking the behavioral activation induced by the D1 agonist. The D1 antagonist SCH23390, administered alone or in combination with the D2 antagonist, produced a modest increase in fetal activity that included mouthing and facial wiping behavior. These data provide evidence that the dopamine system is functional and capable of mediating behavioral effects in the near-term rat fetus. Further, manipulation of dopamine receptors results in a different pattern of behavioral effects than has been reported in older animals. The observation that fetal behavior is influenced by these pharmacological challenges suggests that drugs of abuse known to affect the dopamine system, such as cocaine, may cause profound changes in fetal behavior in utero that could consequently lead to alterations in behavioral and CNS development.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Modulation of dopamine binding in the fetal rat: effects of milk and exogenous opioid manipulation.

Presentation of milk to the newborn rat promotes changes in sensory and motor behavior and concomitant changes in both endogenous opioid and dopamine systems. The present study employed an in vivo binding technique with a tritiated ligand for the D2 receptor ([3H]raclopride) to examine the effects of intraoral milk infusion and opioid manipulations on dopamine activity in the term rat fetus (E21). In Experiment 1, fetuses received a series of milk infusion, which resulted in decreased occupancy at D2 receptors by the endogenous ligand, dopamine, in striatal, septal, and hypothalamic brain regions. In Experiment 2, fetuses were pretreated with morphine, the mu-agonist [D-Ala2,NMe-Phe4,Gly5-ol]-enkephalin (DAMGO), the kappa-agonist U50,488, or saline. Opioid manipulations had no effect on binding at D2 receptors. These results confirm that intraoral milk infusion can modulate activity in the dopamine system of the near-term fetal rat.

Animals↗

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.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

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 (a) the influence of morphine on fetal responsiveness to a single chemosensory infusion, (b) the effect of naloxone blockade of endogenous opioid activity on diminished fetal responsiveness over a series of chemosensory infusions, (c) the effect of endogenous opioids on the recovery of fetal responsiveness to infusion after various dishabituation procedures, and (d) 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.

Animals↗

Cocaine alters behavior in the rat fetus.

Changes in motor behavior and sensory responsiveness were characterized in rat fetuses on gestational Day 21 after acute administration of various doses of cocaine. An increase in fetal motor activity was evident in the 3 highest doses (5, 10, and 20 mg/kg). Cocaine-exposed Ss showed reduced facial wiping in behavioral bioassays of cutaneous sensitivity (10 and 20 mg/kg) and chemosensory responsiveness (20 mg/kg). Changes in other behavioral measures indicated that fetuses detected and responded to these stimuli, suggesting that reduced facial wiping was due to a disruption of sensorimotor integration or motor coordination. Study of the fetus in vivo can provide insights into the mechanisms of cocaine's deleterious effects on central nervous system and behavioral development.

Animals↗

Conditioned opioid activity in the rat fetus.

Classical conditioning in the rat fetus (Embryonic Day 20) was investigated in 4 experiments. Reexposure to a conditioned stimulus (CS; sucrose), after 3 pairings with an unconditioned stimulus (US; milk), reduced fetal facial wiping in a bioassay of perioral cutaneous responsiveness. Reduced responsiveness was evident only in subjects that received paired presentations of the CS and US and cannot be attributed to habituation, sensitization to the CS, or protracted effects of US exposure during conditioning trials. Fetuses attended to the chemosensory, not the tactile, qualities of the sucrose infusion during CS reexposure. Changes in fetal responsiveness resulted from conditioned activity in the endogenous opioid system, specifically at mu opioid receptors. These data confirm that the rat fetus is capable of exhibiting a conditioned opioid response in utero.

Animals↗

Müller cells in vascular and avascular retinae: a survey of seven mammals.

Eight monoclonal antibodies were used to label Müller cells in four mammals that have vascular retinae (cats, dogs, humans, and rats) and in three with avascular retinae (echidnas, guinea pigs, and rabbits). Müller cells were found to have a fairly uniform retinal distribution in seven species, with a mean density of 8,000-13,000 cells mm-2. Müller cells in avascular retinae differ from their vascular counterparts in four respects. First, they are shorter than those in vascular retinae. This difference is mainly due to a reduction in the thickness of the outer nuclear layer. Second, the trunks of Müller cells in avascular retinae tend to be thicker, although those in echidnas are an exception to this trend. Third, Müller cell rootlets in avascular retinae follow a more tortuous course than those in vascular retinae, reflecting the fact that photoreceptor nuclei in the two types of retina have different shapes and stacking patterns. Fourth, due to a reduction in the density of photoreceptors in avascular retinae, there are fewer neurones per Müller cell. Although these four features may enable Müller cells to assist the nutrition of neurones in the inner layers of avascular retinae, they are unlikely to be morphological specializations that have evolved for that purpose. Rather, these features appear to be a direct consequence of the fact that avascular retinae are thinner and have a differently organised outer nuclear layer. These features aside, Müller cells in avascular retinae closely resemble their counterparts in vascular retinae.

Animals↗

Effect of milk on dopamine release in the newborn rat: an in vivo microdialysis study.

Newborn rats exhibit a rich behavioral repertoire to access the nipple and obtain milk. In older pups, catecholamines including dopamine (DA) mediate the behavioral effects of milk. In the present study, pups were delivered at term by caesarean section and instrumented with the microdialysis probe. Microdialysis samples were collected at 15 min intervals and K(+)-evoked levels of DA were measured with HPLC-ED. Pups received either no infusion, single or multiple intraoral infusions of saline or milk during subsequent samples. A decrease in K(+)-evoked DA release was evident after the first infusion in all subjects. Repeated milk infusions continued to reduce levels of extracellular DA, which remained evident 30 min after the last milk infusion. The rat neonate's first exposure to milk exerts lasting effects on neostriatal DA activity in the absence of prior suckling experience.

Administration, Oral↗

Development of catecholaminergic, indoleamine-accumulating and NADPH-diaphorase amacrine cells in rabbit retinae.

We have investigated the ontogeny of four classes of amacrine cells in the rabbit retina. In particular, the distribution, number, soma diameter, dendritic field diameter, and pattern of dendritic stratification were studied in catecholaminergic (CA) and indoleamine-accumulating (IA) amacrines and in two classes of nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase amacrine cells. The first CA and IA cells are observed on the 27th postconceptional day (27PCD) and the first NADPH-diaphorase cells on 28PCD. These first cells are concentrated in the central part of the visual streak, and at subsequent ages, cells in this part of the streak have larger somata and more mature dendritic fields than those elsewhere, supporting the notion that the peak density region is a developmentally advanced part of the retina. Throughout development, amacrine cells of all classes are concentrated in the visual streak, with their density reaching minima at the superior and inferior retinal margins. As their total number increases, the difference in cell density between the streak and the periphery decreases, presumably because proportionately more cells are added at the periphery. Their total number peaks around 42PCD, followed by a decline of 12-31% to adult values. Once the peak number of cells has been reached, the difference in cell density between the streak and periphery begins to increase. The rate of this increase is closely correlated with the increase in retinal area. This redistribution of amacrine cells, as well as a greater expansion of their dendritic fields in peripheral retina, is almost certainly the product of nonuniform retinal expansion.

Aging↗

Organization of the stretch response to milk in the rat fetus.

Intraoral infusion of milk reliably elicits a stretch response in the rat fetus. The fetal stretch response appears isomorphic to the stereotypic behavior exhibited postnatally by suckling rat pups during milk ejection. Using a procedure that permits direct fetal observation, milk infusions were delivered to rat fetuses on Day 20 or 21 of gestation. Infusion of milk promoted systematic changes in fetal behavior that culminated in expression of the stretch response nearly 3 min later. Interruption of this behavioral sequence prevented stretching, suggesting that a period of behavioral reorganization after milk infusion is necessary but not sufficient for the stretch response to occur. The behavioral sequence initiated by the fetal rat's first exposure to milk is remarkably similar to the behavior exhibited by experienced infant rats at the nipple.

Animals↗

Oral capture and grasping of an artificial nipple by rat fetuses.

Although born blind and deaf, newborn rats exhibit a remarkable capacity to recognize and gain access to the nipples of the lactating mother. However, it is well-known that full-term rat neonates will not attach to an artificial nipple. In the present study, an artificial nipple fashioned from soft vinyl was presented to rat fetuses from E17-E21 of gestation. Fetuses showed side-to-side head movements that resulted in oral capture of the nipple on E18 and exhibited a direct nipple-grasping response from E19 through term. Frame-by-frame analysis of videotape records of E21 rat fetuses revealed that tactile contact with the artificial nipple elicited mouthing, licking directed at the nipple, forelimb treadling, and grasping of the nipple. Fetuses also exhibited components of aversive behavior, including facial wiping and head turning, that appeared to terminate oral contact with the nipple. Morphine pretreatment reduced the expression of aversive responses and promoted licking and grasping of the artificial nipple. In addition to documenting the prenatal ontogeny of this important neonatal behavior, these findings imply a role for endogenous opioids in the newborn rat's first suckling episode.

Animals↗

Fundamental motor patterns of the mammalian fetus.

Techniques that permit direct observation of fetuses in vivo recently have expanded our understanding of prenatal behavioral development in mammals. Although fetal motor activity seems to lack the dynamic, goal-directed character of postnatal behavior, the dimensions that define behavioral organization after birth are applicable to the movements expressed by fetuses. Fetal activity exhibits temporal, sequential, and spatial organization that emerges between the inception of movement and term. Fetal rodents, for example, exhibit coordinated motor patterns antecedent to postnatal righting, locomotion, suckling, maternal-infant communication and grooming behavior, while other action patterns appear to be functional adaptations to the intrauterine niche. Fetuses also are behaviorally responsive to sensory stimulation and changes in environmental conditions in utero. Expression of these behavioral properties emphasizes continuity between prenatal and postnatal life while implying an adaptive role for behavior before birth.

Animals↗

Effects of recalled childhood gender nonconformity on adult genitoerotic role and AIDS exposure. HNRC Group.

The connections between childhood gender nonconformity (assessed by the Freund Feminine Gender Identity Scale, or FGI) and adult genitoerotic role (assessed by a sex history) were examined. The core sample was a group of 106 men who had sex with other men before 1980 and who are currently enrolled in two longitudinal studies of AIDS. Although other workers have cautioned against assuming a priori that childhood gender role is inherently related to adult preferences for particular sexual acts, our data suggest that there is at least a statistical association between these two concepts. In particular, the FGI (and many of its factors and items) are significantly associated with preferences for receptive anal intercourse and, less clearly, with oral-anal contact--but not with oral-genital intercourse or insertive and intercourse. Suggestions for AIDS prevention and safe-sex awareness are made on the basis of these findings. The data also suggest that in sex research involving homosexual men, the correct genitoerotic role distinction is not insertive vs. receptive behaviors, or even insertive vs. receptive and intercourse, but receptive anal intercourse vs. all other behaviors.

Acquired Immunodeficiency Syndrome↗

Fetal heart rate response to milk predicts expression of the stretch response.

On the day before birth, rat fetuses respond to an intraoral infusion of milk with a stretch response that resembles the behavior of suckling pups at the nipple. Unlike the postnatal response, which occurs coincident with milk ejection, the fetal stretch occurs 3-5 min after milk infusion. Measurement of fetal heart rate (HR) is useful as a predictor of the fetal stretch response. Expression of the stretch response was preceded by a reduction in HR variability and a transient episode of bradycardia. Fetuses that did not stretch showed a delayed reduction in HR variability and no evidence of HR deceleration. Systematic changes in fetal HR may be indicative of changes in fetal state associated with milk infusion and the stretch response.

Animals↗

Dimethyl disulfide mimics the effects of milk on fetal behavior and responsiveness to cutaneous stimuli.

This study examined the behavioral responses of near-term rat fetuses to a range of chemosensory fluids that resemble constituents of milk or are present in the context of suckling immediately after birth. Milk and dimethyl disulfide (DMDS), a constituent of pup saliva that promotes postnatal nipple attachment, were effective in altering fetal motor activity (increased mouthing and rearlimb movements after infusion), and producing changes in fetal responsiveness to perioral cutaneous stimulation (reduced incidence of facial wiping). The behavioral effects of DMDS were reversed by naloxone and the kappa receptor antagonist nor-binaltorphimine diHCl, suggesting kappa opioid involvement in these behavioral changes. The existence of prenatal responsiveness to DMDS suggests that this substance may function as a semiochemical during the neonatal period.

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Behavioral response of altricial and precocial rodent fetuses to acute umbilical cord compression.

Norway rat fetuses (Rattus norvegicus) exhibit a stereotypic behavioral response when the umbilical cord is experimentally compressed with a vascular clamp. In this study, the development of the fetal behavioral response to cord compression was compared in altricial and precocial rodents, which differ markedly in neural and motor maturity at the time of birth. Both altricial and precocial species showed some form of behavioral response to umbilical cord compression. Fetuses of two altricial species, Norway rats and Mongolian gerbils (Meriones unguiculatus), expressed hyperactivity in response to cord compression throughout the last third of gestation. In contrast, precocial cotton rats (Sigmodon hispidus) and spiny mice (Acomys cahirinus) did not respond to cord compression until relatively late in gestation. Thus, altricial and precocial species do not express the cord compression response during comparable periods of neural development: precocial species are much more mature at the earliest expression of this behavior than altricial species. These findings are consistent with the interpretation that the cord compression response is a behavioral adaptation that can promote survival of the fetus in utero.

Animals↗