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Biomedical subjects

R H Porter

Publications and source records attributed to R H Porter.

At least 19 recordsLinked to original sources
PubMed2004

The biological significance of skin-to-skin contact and maternal odours.

UNLABELLED: Infant-mother bodily contact is believed to be the species-typical pattern of immediate postpartum child care. Mothers and newborns engage in mutually beneficial interactions. Maternal odours stimulate breastfeeding activity and are implicated in individual recognition. CONCLUSION: Skin-to-skin contact and exposure to maternal odours facilitate infants' adaptation to the early postnatal environment.

Breast Feeding↗
PubMed2002

Induction of maternal behavior in non-parturient adoptive mares.

An attempt was made to elicit maternal behavior in non-parturient Welsh pony mares through a combination of hormonal treatment and vaginal-cervical stimulation (VCS). Lactation was induced in 16 nonpregnant, non-parturient mares via a combination of estradiol, progesterone and a dopamine antagonist (sulpiride). During the adoption trials, each lactating mare was confined behind a padded bar and a newborn foal was held near her head. Eight of the mares received two 3-min periods of VCS when the foster foal was introduced. Following VCS, the foal was released and its interactions with the adoptive mare observed until the acceptance criterion was met (i.e. the mare accepted the foal at the udder with no signs of aggression). The remaining eight adoptive mares were treated in the same manner but did not receive VCS. All 16 non-parturient mares eventually accepted and nursed their adopted foal. However, acceptance latencies were significantly shorter for mares in the VCS condition than for those without VCS, and did not differ between the VCS condition and a group of control mares with their biological offspring. In subsequent choice tests, both groups of foster mares (with/without VCS), like the control mares, displayed a preference for their 'own' foal. Once the non-parturient mares accepted their foster foal, their maternal behavior resembled that of control mothers. The positive effect of VCS on maternal acceptance may reflect a release of oxytocin triggered by this treatment.

Administration, Topical↗
PubMed2001

Agonist-induced functional desensitization of recombinant human 5-HT2 receptors expressed in CHO-K1 cells.

The desensitization characteristics of recombinant human 5-HT(2A), 5-HT(2B), and 5-HT(2C) receptors (VSV and INI isoforms) stably expressed in CHO-K1 (Chinese hamster ovary) cells was investigated by calcium fluorimetry. Comparative desensitization characteristics of the agonists 5-HT, m-chlorophenylpiperazine (mCPP), and 2,5-dimethoxy-4-iodoamphetamine hydrobromide (DOI) were performed. Human 5-HT(2C (INI)) receptors exhibited a greater degree of desensitization to all agonists tested than edited 5-HT(2C (VSV)) receptors. A 2-hr exposure to 5-HT resulted in a significantly larger reduction in response upon re-exposure to 5-HT at 5-HT(2C (INI)) receptors, as compared to 5-HT(2C (VSV)) receptors (72% and 47% respectively, P < 0.01). Both receptor isoforms were expressed at similar densities. Human 5-HT(2B) receptors exhibited the most dramatic degree of desensitization, with prior exposure to 5-HT reducing subsequent response to 5-HT by 80%, with an extremely rapid time-course (t(1/2) < 5 min). The response at 5-HT(2A) receptors was reduced by 54%. The partial agonists mCPP and DOI also elicited desensitization, generally in line with their relative efficacies at each receptor, but exhibited more rapid kinetic profiles than 5-HT. Heterologous desensitization of an endogenously expressed G(q/11)-coupled purinergic receptor was also examined following preincubation of the cell lines with 10 microM 5-HT. Only stimulation of 5-HT(2C (VSV)) receptors resulted in a profound attenuation of subsequent ATP mediated responses. These results demonstrate differing degrees of both homologous and heterologous desensitization of 5-HT(2) receptors. Additionally, the different desensitization profiles of 5-HT(2C (INI)) and 5-HT(2C (VSV)) receptor may be due to signal transduction differences caused by RNA editing.

Animals↗
PubMed2001

Characterisation of agonist binding on human 5-HT2C receptor isoforms.

The 5-HT2C receptor is expressed in different isoforms as a result of mRNA editing. Both INI (unedited) and VSV (a fully edited version) isoforms are abundant in rat brain. The VSV isoform lacks the high affinity recognition site for 5-HT, which may be caused by low efficiency coupling to G-proteins. In this study we have investigated the pharmacology of the agonist binding site of these two isoforms of the 5-HT2C receptor. The VSV isoform was expressed in Chinese hamster ovary cells (CHO) and the INI isoform in both Chinese hamster ovary cells and human embryonic kidney cells (HEK-293). Saturation analysis using [3H]5-HT revealed high and low affinity recognition sites on the INI isoform in both cell types whilst the VSV isoform did not have the high affinity binding site for [3H]5-HT. Displacement studies were undertaken using [3H]5-HT to label the receptors. In these studies the affinity of agonists (5-HT, Ro600175 ((S)-2-(6-Chloro-5-fluoroindol-1-yl)-1-methylethylamine), MK212 (6-Chloro-2-(piperazinyl) pyrazine), mCPP (1-(m-chlorophenyl)-piperazine), TfMPP (N-(m-trifluoromethylphenyl)piperazine), DOI (1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane), DOB (1-(4-bromo-2,5-dimethoxyphenyl)-2-aminopropane) and 8OH-DPAT (8-hydroxy-2-(di-N-propylamino)tetralin) was higher at the INI isoform, whilst antagonist affinity (ketanserin and mesulergine) did not change between the two receptor isoforms. There were no differences between the INI isoform expressed in the CHO and HEK-293. This suggests that the INI isoform of the 5-HT2C receptor is pharmacologically similar to the VSV form of the 5-HT2C receptor but that it couples more efficiently to G-proteins.

Animals↗
PubMed2001

Breast odour as the only maternal stimulus elicits crawling towards the odour source.

UNLABELLED: In previous studies, newborn infants placed on their mother's chest grasped a nipple and sucked without assistance. Furthermore, neonates sucked preferentially from an untreated breast rather than the alternative breast that had been washed to eliminate its natural odour. This study investigated the influence of breast odours per se on orientated physical movement of neonates. In total, 22 babies were observed during two trials on a warming bed. In one trial, a pad carrying the mother's breast odour was placed 17 cm in front of the baby's nose; in the other trial a clean pad was used. More babies moved towards and reached the breast pad than the clean pad. CONCLUSION: Natural breast odous unsupported by other maternal stimuli therefore appear to be sufficient to attract and guide neonates to the odour source.

Breast↗
PubMed2000

Characterization of iodoacetate-mediated neurotoxicity in vitro using primary cultures of rat cerebellar granule cells.

The neuroprotective efficacy of antioxidant molecules against iodoacetate (IAA) neurotoxicity in rat cerebellar granule cell (CGC) cultures was investigated. Transient exposure to IAA caused a concentration-dependent decrease in cell viability (ED50 = 9.8 microM). Dizocilpine maleate (MK-801), and 1,2,3,4-tetrahydro-6-nitro-2,3-dioxobenzo[f]quinoxaline-7-sulfonamide (NBQX), failed to prevent IAA toxicity. Certain antioxidant molecules were shown to be neuroprotective against IAA when combined with MK-801 but were ineffective when administered alone. (S)-(-)-Trolox, butylated hydroxytoluene (BHT), and U-83836E exhibited EC50 values of 78, 5.9, and 0.25 microM, respectively, in the presence of 10 microM MK-801. IAA also induced an increase in intracellular oxidative stress, which was quenched by the antioxidants (in the presence of MK-801) in cultures loaded with the oxidant sensitive dye 2'7'-dichlorodihydrofluorescein diacetate (DCFH-DA).

Animals↗
PubMed2000

Comparative effects of continuous infusion of mCPP, Ro 60-0175 and d-fenfluramine on food intake, water intake, body weight and locomotor activity in rats.

1. The aim of the study was to compare the effects of 14 day subcutaneous infusion of the 5-HT(2C) receptor agonists, m-chlorophenylpiperazine (mCPP, 12 mg kg(-1) day(-1)) and Ro 60-0175 (36 mg kg(-1) day(-1)) and the 5-HT releasing agent and re-uptake inhibitor, d-fenfluramine (6 mg kg(-1) day(-1)), on food and water intake, body weight gain and locomotion in lean male Lister hooded rats. 2. Chronic infusion of all three drugs significantly reduced food intake and attenuated body weight gain. In contrast, drug infusion did not lead to significant reductions in locomotor activity in animals assessed 2 and 13 days after pump implantation. 3. In a subsequent 14 day study that was designed to identify possible tolerance during days 7 - 14, animals were given a subcutaneous infusion of mCPP (12 mg kg(-1) day(-1)) or d-fenfluramine (6 mg kg(-1) day(-1)) for either 7 or 14 days. During the first 7 days both drugs significantly reduced body weight gain compared to saline-infused controls; however, from day 7 onwards animals withdrawn from drug treatment exhibited an increase in body weight such that by day 14 they were significantly heavier than their 14-day drug-treated counterparts. 4. Both mCPP and d-fenfluramine reduced daily food intake throughout the infusion periods. For 14-day treated animals this hypophagia was marked during the initial week of the study but only minor during the second week. In light of the sustained drug effect on body weight, the data suggest that weight loss by 5-HT(2C) receptor stimulation may be only partly dependent on changes in food consumption and that 5-HT(2C) receptor agonists may have effects on thermogenesis. 5. These data suggest tolerance does not develop to the effects of d-fenfluramine, mCPP and Ro 60-0175 on rat body weight gain.

Analysis of Variance↗
PubMed2000

GluR1 glutamate receptor subunit is regulated differentially in the primate basal ganglia following nigrostriatal dopamine denervation.

Nigrostriatal dopaminergic denervation is associated with complex changes in the functional and neurochemical anatomy of the basal ganglia. The excitatory neurotransmitter glutamate mediates neural signaling at crucial points of this circuitry, and glutamate receptors are differentially distributed in the basal ganglia. Available evidence suggests that the glutamatergic corticostriatal and subthalamofugal pathways become overactive after nigrostriatal dopamine depletion. In this study, we have analyzed the regulation of the GluR1 subunit of the a-amino-3-hydroxy-5-methyl-4-isoxazole propionate glutamate receptor in the basal ganglia of primates following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopamine denervation. The dopamine denervation resulted in distinct alterations in GluR1 distribution: (1) GluR1 protein expression was markedly increased in caudate and putamen, and this was most pronounced in the striosomes; (2) GluR1 protein was altered minimally in subthalamic nucleus; (3) expression of GluR1 was down-regulated in the globus pallidus by 63% and in the substantia nigra by 57%. The down-regulation of GluR1 expression in the output nuclei of the basal ganglia, the internal segment of the globus pallidus and the substantia nigra pars reticulata, may be a compensation for the overactive glutamatergic input from subthalamic nucleus, which arises after striatal dopamine denervation. Our results indicate that the glutamatergic system undergoes regulatory changes in response to altered basal ganglia activity in a primate model of Parkinson's disease. Targeted manipulation of the glutamatergic system may be a viable approach to the symptomatic treatment of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2000

Role of mother-young interactions in the survival of offspring in domestic mammals.

The defining characteristic of mammals is that females nurse and care for their young; without this, the neonate has no chance to survive. Studies on wild and domestic species show that the neonatal period is the most critical step in the lifetime of a mammal. This review compares three well-studied species (the rabbit, pig and sheep) that differ in their parental strategies and in the problems that neonates have to overcome. As a general trend, mother-young interactions vary according to the maturity of the newborn, and the size of the litter. Neonatal survival relies to a great extent on an environment that is ecologically appropriate for the developmental stage of the neonate, and on optimum interactions with the mother. Adaptive maternal care supposes that the mother provides the basic needs of the neonate: warmth (in pigs and rabbits) or shelter, food, water and immunological protection (via colostrum) and, in some instances, protection from predators and other conspecifics. A major risk facing all neonates, other than the birth process itself, is inadequate colostrum intake owing to delayed suckling or competition with siblings, which leads to starvation, hypothermia or even crushing, as has been observed in pigs.

Animals↗
PubMed1999

A simple method for testing odor detection and discrimination in chicks.

A simple procedure for testing newly hatched chicks' responses to olfactory stimuli is described. Chicks that were hand held under a heatlamp became inactive and closed their eyes (as if asleep) within 2 min. Sleeping chicks displayed overt behavioral responses to an odorized q-tip (head shaking, beak clapping) that were not observed in awake chicks. Sleeping latencies were shorter for 1-day-old chicks that had been food deprived prior to testing than for chicks that had ad lib access to food and water. When airborne odors were presented by squeezing a soft plastic odor bottle near the beak, sleeping chicks' reactions to mint were of a greater magnitude than their responses to lavender or orange scents. Nonetheless, all three odors elicited more pronounced behavioral responses than did the water control stimulus. This method allows rapid testing of individual chicks for odor detection and discrimination.

Analysis of Variance↗
PubMed1999

Unique salience of maternal breast odors for newborn infants.

Human infants are particularly responsive to olfactory cues emanating from their mother's nipple/areola region. Beginning within minutes after birth, maternal breast odors elicit preferential head orientation by neonates and help guide them to the nipple. Such odors also influence babies' general motor activity and arousal, which may contribute further to successful nipple localization and sucking. The role of maternal olfactory signals in the mediation of early breast-feeding is functionally analogous to that of nipple-search pheromone as described in nonhuman mammals. To some extent, the chemical profile of breast secretions overlaps with that of amniotic fluid. Therefore, early postnatal attraction to odors associated with the nipple/areola may reflect prenatal exposure and familiarization. Although newborns are generally attracted to breast odors produced by lactating women, breast-fed infants rapidly learn their mother's characteristic olfactory signature while sucking at her breasts and can subsequently recognize her by that unique scent alone. Early odor-based recognition may be an important factor in the development of the infant-mother bond.

Animals↗
PubMed1999

Functional characterization of agonists at recombinant human 5-HT2A, 5-HT2B and 5-HT2C receptors in CHO-K1 cells.

1. The goal of this study was to characterize the agonist pharmacology of human 5-HT2A, 5-HT2B and 5-HT2C (VSV) receptors expressed in CHO-K1 (Chinese hamster ovary) cells. 2. We used a fluorometric imaging plate reader (FLIPR) which allows rapid detection of rises in intracellular calcium levels upon the addition of agonists. 3. Stimulation of all three receptors by 5-HT caused a robust concentration dependent increase in intracellular calcium levels. No such effect was observed from non-transfected control CHO-K1 cells. 4. The rank order of potency of agonists at the different receptor subtypes varied. Tryptamines, BW-723C86, d-norfenfluramine, Ro 60-0175 and LSD exhibited the following rank order of potency; 5-HT2B>5-HT2C>5-HT2A. Piperazines such as m-Chlorophenylpiperazine (mCPP), ORG-12962, MK-212 and also ORG-37684 exhibited a rank order of potency of 5-HT2C>5-HT2B>5-HT2A. The phenylisopropylamines DOI and DOB had a rank order of 5-HT2A>5-HT2B>5-HT2C. 5. Many agonists tested had partial agonist actions when compared to 5-HT, and a wide range of relative efficacies were exhibited, which was cell line dependent. For example, mCPP had a relative efficacy of 65% at 5-HT2C receptors but <25% at either 5-HT2A or 5-HT2B receptors. 6. Interpretation of literature values of functional assays using different cell lines, different receptor expression levels and different receptor isoforms, is complex. Species differences and the previous use of antagonist radioligands to characterize agonist potency in binding assays emphasizes the importance of studying agonists in the same experiment using the same assay conditions and parental cell lines.

Animals↗
PubMed1998

Soothing effect of amniotic fluid smell in newborn infants.

Newborn young of several mammalian species are attracted to the odor of amniotic fluid (AF); these chemical cues also appear to calm neonates and help them adapt to their novel postnatal environment. AF odor likewise elicits positive (head orientation) responses by human infants. The present study systematically examined whether the odors of AF and mother's breasts influence the crying of the newborn infant, when separated from its mother. The total crying time from 31-90 min postnatal was registered on tapes in 47 healthy fullterm newborns, allocated to one of three conditions; exposure to either AF or breast odor or no exposure (controls). Babies exposed to AF smell cried significantly less (median 29 s) than babies in the two other groups (breast odor--301 s, controls--135 s). The data are consistent with the hypothesis that the fetus may become familiar with chemical cues present in the intrauterine environment. Our data provide new evidence of the human baby's fine olfactory discrimination capacity, and add to the growing body of evidence indicating that naturally occurring odors play an important role in the mediation of infants' early behavior.

Amniotic Fluid↗
PubMed1998

Olfaction and human neonatal behaviour: clinical implications.

About 1-2% of the human genome is allocated to production of receptors for the olfactory epithelium--a hint as to the possible importance of this chemical sense, which includes two anatomically distinct systems: the main olfactory system with sensory cells located in the upper part of the nasal cavity, and the vomero-nasal organ with sensory cells on the nasal septum. In adults, individual odours may influence mate preferences and a growing body of evidence indicates that naturally occurring odours play an important role in the mediation of the infant's behaviour. Even foetal olfactory learning seems to occur and breast odours from the mother exert a pheromone-like effect at the newborn's first attempt to locate the nipple. Newborns are generally responsive to breast odours produced by lactating women. Olfactory recognition may be implicated in the early stages of the mother-infant attachment process, when the newborns learn to recognize the own mother's unique odour signature--a process possibly facilitated by the high norepinephrine release and the arousal of the locus coeruleus at birth. New knowledge about human odour physiology may have diagnostic and therapeutic implications--the initiation and stabilization of breastfeeding and termination of apnoeic spells are mentioned as examples.

Adult↗
PubMed1997

Distribution of kainate receptor subunit mRNAs in human hippocampus, neocortex and cerebellum, and bilateral reduction of hippocampal GluR6 and KA2 transcripts in schizophrenia.

The mRNAs encoding kainic acid (KA) preferring glutamate receptor subunits (GluR5-7, KA1 and KA2) are differentially expressed in rat brain. We have used regional and cellular in situ hybridization histochemistry with subunit-specific 35S-labelled oligodeoxyribonucleotides to examine these mRNAs in adult human hippocampus, neocortex and cerebellum. GluR5 mRNA was detected only in Purkinje cells and a few scattered hippocampal neurons. GluR6 mRNA was relatively abundant in all areas, notably in dentate gyrus, pyramidal neurons of CA3, and cerebellar granule cells, as well as being present in superficial and deep laminae of the neocortex. Moderate signal for GluR7 mRNA was seen in deep laminae of the neocortex with a weak signal in the dentate gyrus; in dipped sections GluR7 mRNA was also apparent over some pyramidal and non-pyramidal cells in hippocampus and over putative cerebellar stellate/basket cells. KA1 mRNA was detected in the dentate gyrus but not reliably elsewhere. The expression profile and abundance of KA2 mRNA was similar to that of GluR6 mRNA. For all five transcripts, concurrent hybridization of rat brain sections produced the anticipated distribution of signal. The data indicate that the regional and cellular distribution of KA receptor subunit mRNAs in human hippocampus, neocortex and cerebellum largely parallels that in the corresponding areas of rat brain, albeit at lower levels, especially with regard to GluR5 and KA1 transcripts. In schizophrenia there is a partial loss of hippocampal non-NMDA receptors, but there are no data concerning KA receptor subunit expression. KA2 and GluR6 mRNAs were sufficiently abundant for a comparison in the left and right hippocampus between 11 schizophrenics and 13 controls. Using film autoradiography, both mRNAs were significantly reduced in the schizophrenics, having controlled for the effects of brain pH, post mortem interval and age. GluR6 mRNA was also quantitated in cerebellum, wherein no differences were found between cases and controls. In conjunction with earlier findings of reduced hippocampal GluR1 and GluR2 expression and a loss of [3H]KA binding sites, these data show that schizophrenia is associated with impaired expression of both AMPA- and KA-preferring ionotropic glutamate receptors. These deficits are likely to contribute to the glutamatergic component of the disease pathophysiology.

Aged↗
PubMed1997

Natural odour preferences of newborn infants change over time.

At their first sucking contact, neonates prefer an unwashed breast to a washed one, but an amniotic fluid (AF)- treated breast over a "natural odour" breast. We examined the development of these neonatal olfactory preferences. On days 3-4 significantly more babies still selected their mother's unwashed breast (n = 21) than the washed alternative (n = 8). Preferences for natural breast odours were more pronounced for girls than boys. In a subsequent experiment comprising another 28 babies, the number of babies who selected a naturally scented (n = 9) vs an AF-treated breast (n = 19) on days 2-5 were not reliably different. However, babies who selected the natural breast had longer pre-test maternal contact and had spent more time breastfeeding. Ten babies who chose the AF breast in the latter experiment were tested in the same manner several days later; all preferred the naturally smelling breast. While preferences for AF fade after birth, responsiveness to natural breast odours may be enhanced by postnatal experience.

Amniotic Fluid↗
PubMed1996

The effect of chronic haloperidol treatment on glutamate receptor subunit (GluR1, GluR2, KA1, KA2, NR1) mRNAs and glutamate binding protein mRNA in rat forebrain.

Antipsychotic (neuroleptic) drugs have effects on the glutamatergic system which include changes in the expression of glutamate receptor subunits. There are, however, no long-term studies. We have investigated the influence of 16 weeks' treatment with haloperidol on eight glutamate receptor mRNAs in dorsolateral striatum, frontoparietal cortex and hippocampus using in situ hybridization histochemistry. The mRNAs targetted were the flip and flop isoforms of GluR1 and GluR2, KA1 and KA2, NR1, and the glutamate binding protein (GBP). The flip isoform of GluR2 was elevated in striatum and cortex, leading to an increase in the GluR2 flip/flop ratio. KA2 mRNA was increased in hippocampus and cortex. GBP mRNA was increased in striatum. The other mRNAs were unaffected. The data show that the profile of glutamate receptor subunit mRNA expression is altered in a molecularly and anatomically selective way following chronic haloperidol administration. They provide another indication of glutamatergic involvement in the biochemical response to antipsychotic medication.

Animals↗