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Biomedical subjects

K M Kendrick

Publications and source records attributed to K M Kendrick.

At least 55 records · Page 3Linked to original sources
PubMed1995

Is the inhibitory action of estradiol on luteinizing hormone pulse frequency in anestrous ewes mediated by noradrenergic neurons in the preoptic area?

This study tested the hypothesis that estradiol inhibits luteinizing hormone (LH) pulse frequency in anestrous ewes by increasing the activity of an inhibitory noradrenergic (NE) system that acts in the ovine preoptic area (POA). The effects of estradiol on the release of NE and other neurotransmitters in the POA were determined using intracranial microdialysis. Microdialysis probes (5 mm membrane length) were inserted via chronic guide tubes into the POA. Ringer's solution was pumped through the probes at a rate of 2 microliters/min for 8 h, the alpha-adrenergic antagonist phenoxybenzamine (PBZ; 60 micrograms/ml of Ringer's solution) was then administered via the probe from hours 8 to 12, and Ringer's solution alone was given the last 4 h. The outflow from the dialysis probes was collected every 20 min from 2 to 16 h and concentrations of aminergic transmitters and gamma aminobutyric acid determined by high-performance liquid chromatography. Blood samples were collected every 10 min throughout the experiment and the LH pulse patterns determined. Dialysis was done in the same neural area twice in each ewe, without (ovariectomy only) and with estradiol treatment (ovariectomy and a 1.5-cm-long Silastic capsule filled with crystalline estradiol placed subcutaneously for 2 days); the order of dialysis was randomized. As expected, estradiol decreased the LH pulse frequency. This negative feedback action of estradiol was associated with a decrease in mean NE concentrations in dialysate samples and an increase in the intra-animal variability of NE. Estradiol had no effect on any other neurotransmitter measured.(ABSTRACT TRUNCATED AT 250 WORDS)

Anestrus↗
PubMed1994

Microdialysis measurement of neurochemical changes in the mediobasal hypothalamus of ovariectomized ewes during oestrus.

Oestrus behaviour and the luteinizing hormone (LH) surge are induced in ovariectomized ewes by oestradiol (E2) after a period of progesterone priming with a low level of E2 (Pge2) and we have previously shown that these effects are primarily mediated through their action on the mediobasal hypothalamus (MBH). The aim of the present study was to assess what neurochemical changes in the MBH are induced by these steroids that might mediate their action on oestrus behaviour and LH release. Eight ovariectomized ewes were implanted with microdialysis probes in the MBH and submitted to three artificial cycles, so that they exhibited either both oestrus behaviour and an LH surge (Pge2 + E2), an LH surge alone (E2 alone) or neither oestrus behaviour nor an LH surge (Pge2 alone). Microdialysis and blood samples were collected every 30 min from 4 h before the end of Pge2 treatment until the end of oestrus. Behavioural tests with a ram were made to assess receptivity. Dopamine (DA) levels were found to increase significantly at the termination of Pge2 treatment after both Pge2 + E2 and Pge2 treatments. When the ewes received E2 after a Pge2 + low estradiol priming (Pge2 + E2), DA levels decreased 16 h later (4 h after E2) whereas they did not change after E2 or Pge2 alone. By contrast, serotonin (5HT) levels did not change significantly during the first 24 h but then increased when ewes received E2 alone and decreased when they were treated with Pge2 + E2. gamma-Aminobutyric acid (GABA) concentrations decreased significantly at the beginning of the sampling period after all treatments but this decrease lasted longer after Pge2 + E2 and was most pronounced at the beginning of receptivity. No significant long term effects of these steroid treatments were found on noradrenaline (NA), aspartate, glutamate, glycine and taurine levels. However, E2 administration was followed during the next few hours by a significant increase in glycine and to a smaller extent in glutamate and GABA. More importantly, when ewes were treated with Pge2 + E2, NA levels increased significantly following the behavioural interactions with a ram when the ewes were sexually receptive. In contrast to this, DA levels only increased during interactions with the ram when the ewes were not receptive. 5HT levels increased after tests where the ewe was either receptive or unreceptive to the male. GABA, aspartate and glycine levels increased in the sample just preceding the test and then decreased during it.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Modulation of in vivo striatal transmitter release by nitric oxide and cyclic GMP.

The effects of nitric oxide (NO) and cyclic GMP on in vivo transmitter release in the rat striatum were investigated using microdialysis sampling in urethane-anaesthetised animals. The NO release-inducing substances S-nitrosoacetylpenicillamine (SNAP), S-nitrosoglutathione (SNOG), and sodium nitroprusside (SNP) increased extracellular concentrations of aspartate (Asp), glutamate (Glu), gamma-aminobutyric acid (GABA), taurine (Tau), acetylcholine (ACh), and serotonin (5-HT). Dopamine (DA) concentrations were decreased by SNAP but were increased by SNOG and SNP. An NO scavenger, haemoglobin, blocked or reduced the effects of SNAP on transmitter release. However, the control carrier compounds for SNAP, SNOG, and SNAP (penicillamine, glutathione, and potassium ferricyanide, respectively, which do not induce release of NO) also increased GABA, Tau, DA, and 5-HT concentrations. When NO gas was given directly by dissolving it in degassed Ringer's solution, DA concentrations decreased significantly, and those of Asp, Glu, GABA, Tau, ACh, and 5-HT increased. These effects of NO gas were all inhibited by coadministration of haemoglobin and for GABA, Tau, ACh, and DA showed some calcium dependency. The cyclic GMP agonists 8-bromo-cyclic GMP and dibutryl-cyclic GMP stimulated dose-dependent increases in Asp, Glu, GABA, Tau, ACh, DA, and 5-HT concentrations. Increased striatal transmitter release in response to NO may therefore be mediated by its stimulatory action on cyclic GMP formation. NO inhibition of DA release may be mediated indirectly through its stimulation of local cholinergic and GABAergic neurones.

Animals↗
PubMed1994

Maternal behaviour in sheep and its neuroendocrine regulation.

Non-parturient sheep, hormonally primed and presented with newborn lambs are, at best, indifferent to them and if approached by the lamb may show violent rejection. However, non-gestant ewes primed with oestrogen and progesterone, but given vaginocervical stimulation, do show a rapid onset in maternal behaviour. This stimulation is ineffective in promoting maternal behaviour with epidural anaesthesia. Vaginocervical stimulation increases the release of oxytocin into cerebrospinal fluid and in-vivo microdialysis has revealed high levels of oxytocin release in limbic brain areas known to be important for maternal behaviour. Oxytocin, when given intraventricularly, produces the full complement of acceptance and suckling behaviour in non-gestant ewes. Although ineffective when given alone, opioids potentiate the release of oxytocin in the limbic brain and increase the intensity of maternal responding, while the opioid receptor blocker, naltrexone, prevents both maternal induction and oxytocin release. This neural basis for maternally motivated behaviour may be equally relevant to human behaviour, although the mechanisms available for addressing these peptidergic systems have clear differences.

Anesthesia, Epidural↗
PubMed1993

Effect of substance P on acetylcholine and dopamine release in the rat striatum: a microdialysis study.

In vivo microdialysis in urethane anaesthetised rats was used to investigate the effects of substance P (SP) on acetylcholine (ACh) and dopamine (DA) release in the rat striatum. Results showed that SP elicited a dose-dependent increase in ACh release between 1 and 50 pmol/l. The rise in ACh release occurred both during SP administration and for up to 60 min after it. Dose-response curves either based on the initial rise in ACh release, or the total duration of increased release, showed a bell shape with 100 fmol/l and 5 nmol/l doses failing to significantly alter release and a 500 pM dose being less effective than 50 pmol/l. In contrast to this, SP did not significantly alter DA release at doses ranging between 100 fmol/l and 5 nmol/l. There was evidence for a strong desensitisation effect of SP administration since after initial treatment with SP subsequent doses of the peptide, even at very high doses, failed to provoke further changes in ACh still showed the expected increase in release in response to a potassium challenge. Physalaemin and neurokinin A increased ACh release with a similar potency to SP at a 50 pmol/l dose whereas neurokinin B and neuropeptide gamma, while increasing ACh release at a 50 pmol/l dose, were less potent than SP. The effect of SP on ACh release is probably mediated via NK-1 receptors since ACh release in response to SP was reduced in a dose dependent manner by the NK-1 receptor antagonists CP-96,345 and RP-67580.

Acetylcholine↗
PubMed1993

Influence of birth and maternal experience on olfactory bulb neurotransmitter release.

The ewe's ability to selectively recognize her lamb depends upon vaginocervical feedback to the brain stimulating an interest in lamb odours. This process is facilitated by previous maternal experience. We have used in vivo microdialysis to measure changes in the release of intrinsic transmitters in the olfactory bulb (glutamate, dopamine and GABA) at parturition to determine if their release profiles differ depending upon the ewe's past maternal olfactory experience. Glutamate and GABA release increased significantly at parturition in multiparous but not primiparous ewes. Dopamine release increased in both groups but mean basal levels of this transmitter were significantly higher in primiparous ewes during the pre-partum period and the first few hours postpartum. The changes in the underlying neural circuitry which determine these differences are established within 6 h of parturition, as revealed by artificial stimulation of the reproductive tract. This procedure renders the system plastic enabling adoption of strange lambs and, contingent, on this, the release of intrinsic transmitters no longer differs between the two groups of ewes. Pharmacological challenges to the olfactory bulb using retrodialysis in nulliparous and multiparous (maternally inexperienced and experienced) ewes produced significant differences between the groups for induction of glutamate and GABA release, but not that of dopamine. K+ challenges produced greater increases in glutamate and GABA release in multiparous than in nulliparous ewes, while dopamine release did not differ with experience. Glutamate receptor blockade produced increases in glutamate ase without changing GABA release.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Effects of parturition and maternal experience on noradrenaline and acetylcholine release in the olfactory bulb of sheep.

Acetylcholine (ACh) and noradrenaline (NA) release in the olfactory bulb (OB) of ewes was monitored using microdialysis. Both ACh and NA release increased at parturition in multiparous but not in primiparous ewes. However, vaginocervical stimulation performed 6 hr postpartum induced an increase of ACh and NA release in both primiparous and multiparous ewes, indicating that a maturation process had occurred. Finally, pharmacological challenges to the ACh and NA inputs revealed differential responsiveness between nulliparous and multiparous nongestant ewes. These results suggest that the first parturition induces changes in neural circuitry involving ACh and NA inputs to the OB.

Acetylcholine↗
PubMed1993

The role of oxytocin release in the mediobasal hypothalamus of the sheep in relation to female sexual receptivity.

In vivo microdialysis and retrodialysis were used to investigate the role of oxytocin (OXY) release in the mediobasal hypothalamus (MBH) of the ewe in the control of sexual receptivity. Initial experiments showed that OXY release was significantly increased in ovariectomized animals treated with progesterone and oestradiol when they were sexually receptive towards males and received intromissions. No such increases were seen during tests where the ewes were receptive but the males were prevented from achieving intromission. By contrast, OXY release was significantly reduced in tests where the ewes were not receptive to the male. In a second experiment artificial vaginocervical stimulation (VCS) was found to significantly increase OXY release when the animals were treated with oestradiol and this effect was potentiated by progesterone priming. OXY release in the MBH was not significantly altered by VCS in the presence of progesterone priming alone. Plasma OXY concentrations were significantly increased by VCS following all three hormone treatments but no one treatment was significantly more effective than another. Noradrenaline release in the MBH was only significantly increased following VCS when progesterone priming was given before oestradiol treatment. No effects of VCS on release of GABA, glutamate or dopamine were seen but their basal concentrations were significantly increased by the combined steroid treatment compared to oestradiol alone. In a third experiment it was found that OXY (10 microM) infused bilaterally into the MBH of receptive ewes, by retrodialysis, significantly decreased sexual receptivity and increased the release of noradrenaline and GABA.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1993

Changes in oxytocin immunoreactivity and mRNA expression in the sheep brain during pregnancy, parturition and lactation and in response to oestrogen and progesterone.

The effects of pregnancy, parturition and lactation and exogenous treatments with oestradiol and progesterone on oxytocin (OXY) immunoreactivity and gene expression in the sheep brain were investigated. Immunocytochemistry was used to demonstrate that increased OXY-immunoreactivity occurred in cells of the paraventricular (PVN) and supraoptic nuclei (SON), the bed nucleus of the stria terminalis (BNST), the anterior commissural nuclei (ACN) and the periventricular part of the medial preoptic area (PvMP). Oxytocin immunoreactive terminals were also seen in the accessory olfactory nucleus, the glomerular and peri-glomerular layers of the olfactory bulb, the lateral septum, the zona incerta and the pars compacta of the substantia nigra. Compared to ovariectomized and late pregnant animals, the intensity of immunoreactivity was increased in all of these oxytocinergic elements at parturition, during lactation and following exogenous treatment with oestradiol. The OXY-immunoreactivity was also more intense in late pregnant animals compared to ovariectomized ones. Quantitative in situ hybridization histochemistry showed that cells in the PVN, SON, BNST and PvMP all showed significantly increased expression of OXY mRNA in animals at parturition and during lactation compared to late pregnant or ovariectomized animals. Expression levels in late pregnant animals were also significantly higher than in ovariectomized ones. Progesterone treatment significantly increased OXY mRNA in the PVN, SON, BNST and PvMP whereas oestradiol treatment was only effective in the PVN, BNST and PvMP. Combined treatment with these steroids did not significantly increase OXY mRNA levels in comparison with their administration alone. These results show that OXY-immunoreactivity and mRNA expression are at their highest in the sheep brain when maternal behaviour is induced. The increased synthesis/storage of the peptide at parturition may be due to changes in circulating concentrations of both progesterone and oestradiol during late pregnancy.

Animals↗
PubMed1993

Changes in pro-opiomelanocortin and pre-proenkephalin mRNA levels in the ovine brain during pregnancy, parturition and lactation and in response to oestrogen and progesterone.

In the female sheep opioids act centrally to influence both oxytocin release and maternal behaviour. We have used in situ hybridization and histochemistry to investigate the changes in mRNA expression of the two opioid precursor genes, pro-opiomelanocortin (POMC) and pre-proenkephalin (PPE), in discrete hypothalamic nuclei as a function of pregnancy, parturition and lactation and following treatment with oestrogen and progesterone. Quantitative in situ hybridization histochemistry demonstrated that POMC mRNA expression in the arcuate nucleus (ARC) decreased at parturition and increased during lactation compared to late pregnant and ovariectomized animals. Oestradiol and progesterone treatments increased POMC mRNA expression compared to ovariectomized controls. Pre-proenkephalin mRNA expression was quantified in three discrete hypothalamic nuclei, the ventromedial nucleus (VMN), the paraventricular nucleus (PVN) and the suprachiasmatic nucleus (SCN). In the VMN, PPE mRNA expression increased during lactation compared to late pregnancy and parturition. Expression levels during late pregnancy and parturition were decreased compared to ovariectomized animals. Oestradiol increased, and progesterone decreased, PPE mRNA levels compared to ovariectomized controls. Combined progesterone followed by oestrogen treatment produced significant increases in PPE mRNA expression. In the PVN, PPE expression increased at parturition compared to late pregnant, lactating and ovariectomized animals. Expression levels in late pregnant animals were decreased compared to lactating or ovariectomized ones. However, sex steroid treatment produced no changes in PPE expression in the PVN. No changes were observed in PPE mRNA expression in the SCN in response to any of the experimental conditions. This data shows that both POMC and PPE mRNA levels are altered in the sheep brain during pregnancy, parturition and lactation and in response to sex steroids, although the direction of the changes is not always the same and in the case of PPE only the VMN and PVN are affected.

Animals↗
PubMed1992

Changes in the sensory processing of olfactory signals induced by birth in sheep.

After giving birth, sheep and many other species form a selective bond with their offspring based on the sense of smell. Processing of olfactory signals is altered to allow the animals to perform this selective recognition. Lamb odors have little effect on either neurotransmitter release or electrical activity of neurons in the olfactory bulb before birth. However, after birth there is an increase in the number of mitral cells, the principal cells of the olfactory bulb, that respond to lamb odors, which is associated with increased cholinergic and noradrenergic neurotransmitter release. Selective recognition of lambs is accompanied by increased activity of a subset of mitral cells and release of glutamate and gamma-aminobutyric acid (GABA) from the dendrodendritic synapses between the mitral and granule cells. The relation between the release of each transmitter after birth also suggests an increased efficacy of glutamate-evoked GABA release.

Animals↗
PubMed1992

Oxytocin, amino acid and monoamine release in the region of the medial preoptic area and bed nucleus of the stria terminalis of the sheep during parturition and suckling.

Microdialysis sampling was used to measure the release of oxytocin (OXY) and monoamine and amino acid transmitters from the region of the medial preoptic area (MPOA) and the bed nucleus of the stria terminalis (BNST) during parturition and suckling in sheep. Results showed that OXY and gamma-aminobutyric acid release increased in both the MPOA and BNST during parturition and suckling. Noradrenaline (NA) release increased in both structures during parturition but not during suckling. Dopamine (DA) release increased in the MPOA and decreased in the BNST during both parturition and suckling. Aspartate release increased in the MPOA during parturition, and the BNST during suckling, and glutamate release increased in the MPOA and BNST at parturition and only in the BNST during suckling. No changes in the release of serotonin or taurine occurred in these structures during parturition or suckling. In a further experiment on 6 estrogen-primed sheep, OXY (10 micrograms/ml) was infused into the MPOA via bilaterally placed microdialysis probes. This treatment inhibited rejection behavior towards lambs, but did not activate positive maternal responses. These OXY infusions also stimulated release of NA. These results show that complex patterns of neurochemical release occur in two closely related areas of the brain, the BNST and MPOA, during parturition when maternal behavior is stimulated. However, while these patterns of release are similar in the two structures, particularly at birth when maternal behavior is stimulated, they are not identical during labor contractions and suckling. The release of oxytocin within the MPOA during parturition may be important for stimulating a reduction in aggression towards lambs, although this action might be mediated via the effect of OXY on NA release.

Amino Acids↗
PubMed1992

Intracerebral oxytocin is important for the onset of maternal behavior in inexperienced ewes delivered under peridural anesthesia.

Measurement of cerebrospinal concentrations of oxytocin (OT) in intact and peridural-anesthetized ewes showed that central release of OT during parturition is inhibited by this anesthesia. Also, observations of maternal behavior and attraction to amniotic fluid (AF) in inexperienced peridural-anesthetized parturient ewes after intracerebroventricular injections of either OT (2 x 10 micrograms) or saline showed that OT infusions increased the proportion of maternal females (2/17 vs. 10/20; p = .01) and attraction to AF. This study confirms that in sheep vaginocervical stimulation activates the oxytocinergic system, which induces the onset of maternal behavior, and that this action is not limited to maternally experienced females.

Anesthesia, Epidural↗
PubMed1991

GABA release in the zona incerta of the sheep in response to the sight and ingestion of food and salt.

In order to establish which neurotransmitters may influence the activity of zona incerta neurones in the sheep which respond selectively to the sight or ingestion of food, we have measured the release of amino acid and monoamine neurotransmitters from this region using microdialysis sampling. Co-ordinates for the placement of microdialysis probes in regions of the zona incerta where cells respond to the sight or ingestion of food were first established by making single-unit extracellular recordings. When animals were food-deprived results showed that release of gamma-aminobutyric acid (GABA) was increased in response to the sight and ingestion of food but not of aspartate, glutamate, taurine, noradrenaline, dopamine or serotonin. This release of GABA was absent when the animals were shown non-food objects or saw or ingested salt solutions. When the same animals were physiologically sodium-depleted GABA release was evoked by the sight and ingestion of salt solutions and release following the sight and ingestion of food was significantly reduced. These results provide further evidence that GABA is an important neurotransmitter in neural circuits controlling the regulation of food intake.

Analysis of Variance↗
PubMed1991

Morphine and corticotrophin-releasing factor potentiate maternal acceptance in multiparous ewes after vaginocervical stimulation.

The effects of intracerebroventricular infusions of morphine, oxytocin, and corticotrophin-releasing factor (CRF) on maternal behaviour alone, or in conjunction with vaginocervical stimulation were determined in both nulliparous and multiparous ovariectomized ewes, primed with oestrogen for 3 days prior to testing. Both plasma and cerebrospinal fluid levels of oxytocin were measured under similar conditions, following CRF and morphine treatments. In nulliparous ewes, i.c.v. oxytocin and morphine reduced rejection behaviours, but neither these treatments nor vaginocervical stimulation promoted proceptive acceptance behaviour. Ewes that were maternally experienced showed increases in acceptance and a reduction of rejection behaviours following vaginocervical stimulation or i.c.v. oxytocin. Morphine and CRF potentiated the effects of vaginocervical stimulation on these behaviours. No treatment influenced oxytocin release per se, but i.c.v. morphine increased both peripheral and central release of oxytocin in response to vaginocervical stimulation. The results show that maternal experience is essential for oxytocin to promote proceptive behaviours and that morphine and CRF potentiate the effects of vaginocervical stimulation on acceptance behaviour. Since morphine also potentiated the release of oxytocin in response to vaginocervical stimulation it is difficult to separate the relative contribution of direct versus indirect effects of opiates in potentiating maternal bonding.

Animals↗