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C D Ingram

Publications and source records attributed to C D Ingram.

At least 55 records · Page 3Linked to original sources
PubMed1997

Reduced response of the hypothalamo-pituitary-adrenal axis to alpha1-agonist stimulation during lactation.

To determine whether altered noradrenergic activation of the hypothalamo-pituitary-adrenal (HPA) axis contributes to the attenuated neuroendocrine response to stress observed during lactation, the effect of intracerebroventricular injection of the alpha1-agonist methoxamine (100 microg) was compared between virgin and lactating rats. Virgin rats showed significant increases in plasma corticosterone after methoxamine, reaching 317 +/- 44 ng/ml at 10 min and remaining significantly elevated for more than 120 min, but lactating rats showed no significant increase in corticosterone levels. Furthermore, methoxamine induced an increase in paraventricular nucleus (PVN) CRF messenger RNA expression in virgin, but not lactating, animals. Both groups of rats exhibited comparable elevations in plasma PRL after methoxamine treatment. Arginine vasopressin messenger RNA expression within the parvocellular PVN was greater in the lactating animals than in the virgin controls, but methoxamine injection was without further effect. Studies performed on ovariectomized virgin rats and ovariectomized rats receiving estradiol or progesterone replacement failed to reproduce the attenuated HPA responses seen after methoxamine treatment, although methoxamine-induced PRL levels were greatly increased by estradiol, probably arising from an effect on hormone synthesis. In vitro electrophysiological recordings of PVN neurons in hypothalamic slices from proestrous virgin and lactating rats showed that 45-52% of neurons in both groups exhibited excitatory responses to 10(-4) M methoxamine, but there was a differential response to 10(-5) M methoxamine, with PVN neurons from lactating animals failing to show a response. These data show a selective down-regulation of alpha1-mediated activation of the HPA axis in lactating animals. This may contribute to the attenuated stress-induced activation of the HPA axis during lactation.

Adrenergic alpha-Agonists↗
PubMed1996

Characterisation of vasopressin V1a binding sites in the ovine olfactory bulb.

In the ewe, [Arg8]vasopressin (AVP) release into the olfactory bulb (OB) modulates transmitter release necessary for the induction of olfactory memory. [3H]AVP binding to a microsomal preparation of ovine OB revealed saturable binding to a single class of high affinity sites (Kd = 2.03 +/- 0.18 nM). The density of binding sites was significantly greater in the lamb than ewe, but did not vary across the adult oestrous cycle. Displacement using AVP analogues showed that their relative affinities for the ovine V1a receptor were identical to the rat hepatic V1a receptor. These data demonstrate a single class of AVP binding sites in the ovine OB and the first pharmacological characterisation of the ovine V1a receptor.

Animals↗
PubMed1996

Region-specific reduction in stress-induced c-fos mRNA expression during pregnancy and lactation.

Hypothalamo-pituitary-adrenal (HPA) responses to stress are dramatically attenuated during lactation. To examine whether this is due to diminished stress-induced activation of specific areas of the brain involved in HPA responses, c-fos mRNA expression was employed as a marker of stress-induced neuronal activation. Regional levels of expression were quantified in female rats exposed to 30 min immobilisation stress during late pregnancy (days 19-21), early lactation (days 3-4) and mid-lactation (days 10-14), and compared with the levels in virgin females. Stress-induced levels of corticosterone were significantly lower in late pregnant and early lactating rats compared with the levels in virgin females, and this correlated with a marked attenuation of stress-induced c-fos mRNA expression in the parvocellular division of the PVN. This reduced activation suggests that neuroendocrine hyporesponsiveness during lactation may arise from an effect on afferent pathways to the PVN. Extrahypothalamic areas known to be important for HPA activation displayed three patterns of c-fos mRNA expression: (i) in the ventral tegmental area, dorsal vagal complex, pyriform cortex and all areas of the hippocampus (CA1, CA2, CA3, dentate gyrus), expression levels did not vary significantly with reproductive status; (ii) in the locus coeruleus (A6 catecholaminergic group), a peak of expression was detected in late pregnant animals; and (iii) in the medial amygdala, ventral part of the lateral septum and cingulate cortex expression was significantly reduced in pregnant and lactating animals, with a nadir in early lactation. The decreased expression of c-fos mRNA in these latter areas correlated with that in the parvocellular PVN, and suggests that their interaction may contribute to the reduced neuroendocrine responses of lactating rats.

Animals↗
PubMed1996

Endogenous opioid control of somatodendritic oxytocin release from the hypothalamic supraoptic and paraventricular nuclei in vitro.

Oxytocin release was measured in a perifusion system from microdissected supraoptic (SO) and paraventricular (PV) nuclei of ovariectomised female rats. An initial period of electrical stimulation (S1) applied through a pair of platinum electrodes evoked an increase in peptide release, however, subsequent periods of stimulation (S2, S3, S4) were increasingly less effective, suggesting depletion of releasable stores. However, addition of the opioid antagonist, naloxone (5 x 10(-5) M), during periods S2 and S3 potentiated this stimulated oxytocin release, indicating the presence of an endogenous opioid inhibition. Tissue from ovariectomised animals pre-treated with progesterone for 3 days showed increased basal secretion but no naloxone-induced potentiation of electrically-stimulated release. However, increasing the naloxone concentration (5 x 10(-5) M) again revealed a potentiation, indicating that progesterone had caused a shift in the effective dose of the antagonist. These data demonstrate that, like their axon terminals in the neurohypophysis, the dendrites of magnocellular oxytocin neurones are under control of endogenous opioids, and that progesterone causes an increase in this opioid tone. This may function to regulate intranuclear oxytocin secretion in the pregnant and periparturient animal.

Animals↗
PubMed1996

Circadian rhythm of neuronal activity in suprachiasmatic nucleus slices from the vasopressin-deficient Brattleboro rat.

In vitro extracellular recordings were made from tissue slices of suprachiasmatic nucleus from homozygous Brattleboro rats which are deficient in vasopressin. A high proportion (56%) of neurons were excited by application of exogenous vasopressin, indicating that the V1 receptors expressed by these neurons were functional. Basal activity of these vasopressin-sensitive neurons showed a marked circadian variation (higher during the subjective light phase) while vasopressin-insensitive neurons showed no significant variation, suggesting the presence of the V1 receptor identifies a population of highly circadian neurons. Suprachiasmatic neurons from both homozygous rats and their heterozygous (vasopressin-containing) litter mates displayed a circadian rhythm of spontaneous (basal) activity, with firing rates declining during the subjective dark phase, indicating that the endogenous pacemaker driving the circadian rhythm was not dependent upon the presence of vasopressin. However, the peak of spontaneous activity displayed during the subjective light phase was significantly lower in the vasopressin-deficient animals. These data show that the presence of endogenous vasopressin within the suprachiasmatic nucleus is not necessary for the generation of the circadian pattern of activity. However, vasopressin does function to amplify the rhythm by its excitatory effect during the light phase.

Animals↗
PubMed1995

A combined immunocytochemical and retrograde tracing study of noradrenergic connections between the caudal medulla and bed nuclei of the stria terminalis.

Region-specific noradrenergic inputs to the bed nuclei of the stria terminalis (BST) from the caudal medulla were studied using combined Fast Blue injections and tyrosine hydroxylase immunoreactivity (TH-ir). Injections into the rostral, dorsal, ventral and lateral BST resulted in predominantly ipsilateral retrograde labelling restricted to the mediodorsal and ventrolateral caudal medulla. Mediodorsal projecting neurones comprised the A2 TH-ir and a second non-aminergic group medial to A2. All ventrolateral retrogradely labelled neurons showed TH-ir and corresponded to A1. Injections into the caudal BST did not label the A2 and very few A1 neurones, indicating a paucity of noradrenergic inputs from this area of the medulla.

Amidines↗
PubMed1995

Electrical recordings of magnocellular supraoptic and paraventricular neurons displaying both oxytocin- and vasopressin-related activity.

In suckled rats, some magnocellular neurons displayed both vasopressin-related phasic activity and oxytocin-related milk ejection bursts. Characteristics of basal activity and interspike intervals resembled those of vasopressin neurons. Bursts were coincident with those of oxytocin neurons and were facilitated by centrally injected oxytocin, but had lower maximum instantaneous frequency and often no after-inhibition. These data provide evidence of magnocellular neurones of mixed electrophysiological phenotype and complement reports of peptide coexistence.

Animals↗
PubMed1995

Mortyn Jones Memorial Lecture. Limbic regions mediating central actions of oxytocin on the milk-ejection reflex in the rat.

Central oxytocin administration has a profound facilitatory effect on the patterning of the milk-ejection reflex in the lactating rat. Lesion and microinjection studies indicate that this action is, in part, mediated via a population of limbic neurones in the bed nuclei of the stria terminalis and ventrolateral septum, which have been shown to possess oxytocin receptors and to be activated by selective oxytocin-receptor agonists in vitro. In vivo electrophysiological recordings reveal that some of these neurones display cyclical activity which is highly correlated to each milk ejection, and are rapidly activated following i.c.v. administration of oxytocin, coincident with the facilitation of milk ejection activity. A hypothetical model is proposed in which this population of limbic neurones serves to gate the activity of a pacemaker which, in turn, coordinates the bursting of hypothalamic magnocellular neurones. The oxytocin innervation of these neurones and their expression of oxytocin receptors increases in the postpartum period, and the resultant enhanced sensitivity leads to a greater facilitatory response during lactation. Inhibitory opioid and noradrenergic inputs which converge on these oxytocin-sensitive neurones may function to switch off the facilitatory circuit during periods of stress. Thus, this population of limbic neurones participates in the regulation of neuroendocrine activity during lactation by providing an appropriate degree of feedback to alter the patterning of the milk-ejection reflex.

Animals↗
PubMed1995

Influence of reproductive state and ovarian steroids on facilitation of the milk-ejection reflex by central oxytocin.

In the rat, the synchronous bursting activity of oxytocin neurones associated with the milk-ejection reflex displays important changes during the peri-partum and lactational periods. The most dramatic of these changes is the appearance of a facilitatory response to centrally-administered oxytocin, involving an increase in the frequency and amplitude of bursting in the oxytocin neurones, as well as elevation of their background activity. Studies of rats at different times in the pre- and post-partum period show that this response first appears on day 3 of lactation. Ovariectomy on day 21 of gestation, or treatment with the anti-oestrogen tamoxifen on day 22, does not prevent the appearance of this response. However, ovariectomy and treatment with ovarian steroids for 3 days prior to parturition can dramatically alter the character of the facilitatory response. Oestradiol treatment causes an early (pre-partum) appearance of the facilitatory response, whereas progesterone causes the appearance of an inhibitory response (reduction in milk-ejection frequency) to central oxytocin. A major target for the central effects of oxytocin are the bed nuclei of the stria terminalis (BST) and modulation of the neuronal responses in this region may, in part, underlie the changing facilitatory effects. In vitro recordings indicate that sensitivity of BST neurones to oxytocin is increased between pregnancy and lactation, and oestradiol treatment enhances responsiveness coincident with the appearance of a facilitatory response. Progesterone pre-treatment also increases the ability of BST neurones to respond to oxytocin in vitro (although less than oestradiol), an unexpected result given the absence of oxytocin-induced facilitation of the milk-ejection reflex in late pregnancy or following progesterone treatment in vivo. In vivo recordings of BST neurones suggest that one explanation of this lack of correlation may reside in the presence of a mechanism which attenuates the excitatory response to oxytocin, perhaps serving to prevent premature expression of the facilitatory action of oxytocin. Collectively, these data show that there are dramatic reproductive state and steroid-dependent changes in the central action of oxytocin on the synchronous bursting of magnocellular oxytocin neurones. These changes, which have important consequences for the optimization of bursting in oxytocin neurones, may involve plasticity of transduction mechanisms in the oxytocin-responsive elements of the limbic system.

Animals↗
PubMed1994

Suppression of suprachiasmatic nucleus neurone activity with a vasopressin receptor antagonist: possible role for endogenous vasopressin in circadian activity cycles in vitro.

Neurones of the rat suprachiasmatic nucleus (SCN) were tested with [Arg8]vasopressin (AVP) and the AVP receptor antagonist, [d(CH2)5,d-Tyr(OEt)2,Val4,Cit8]-vasopressin in vitro. 52% of AVP-responsive neurones showed an antagonist-induced decrease in activity, indicative of the presence of an endogenous excitatory tone. The magnitude of this effect declined significantly between subjective light and dark phases, consistent with the possibility that circadian fluctuations in endogenous AVP excitation contribute to the cycle of electrical activity within the SCN. However, similar fluctuations in basal activity between the light and dark phases was observed for both antagonist-sensitive and -insensitive neurones, indicating that endogenous AVP was not the only factor determining the circadian cycle.

Animals↗
PubMed1994

The effects of [Arg8]vasopressin and [Arg8]vasotocin on the firing rate of suprachiasmatic neurons in vitro.

The excitatory effect of [Arg8]-vasopressin and its potential contribution to the circadian cycle of electrical activity in the suprachiasmatic nucleus of the rat was investigated using extracellular recordings from hypothalamic slices from virgin female rats. The majority of neurons tested for their responses to vasopressin and [Arg8]-vasotocin displayed coincident, dose-dependent excitation by both peptides, although the relative efficacy varied between neurons, with some showing a highly preferential excitation by vasotocin. Perifusion with the vasopressin receptor antagonist d(CH2)5[Tyr(OEt)2,Val4,Cit8]-vasopressin was able to block the majority of responses to vasopressin or vasotocin (20/25), and similar excitation could be induced by the selective agonist [Phe2,Orn8]-vasotocin, indicating a mainly V1 receptor-mediated effect. Few neurons (3/27; 11%) responded to the oxytocin-specific agonist, [Thr4,Gly7]-oxytocin, suggesting a low occurrence of oxytocin receptors. In addition to blocking the action of exogenous vasopressin, the V1 antagonist caused a reversible suppression of spontaneous basal activity in 7/25 cases, consistent with the presence of an endogenous excitatory vasopressin tone. In agreement with previous reports, the activity of suprachiasmatic nucleus neurons showed a significant correlation between spontaneous activity and the light-dark cycle, with activity decreasing during the subjective dark phase. When neurons were divided on the basis of their response to vasopressin and/or vasotocin, the peptide-sensitive neurons continued to show a strong correlation (r = 0.513, P < 0.01) while the insensitive neurons showed no correlation (r = 0.136, P > 0.05). These data confirm the presence of V1 type receptors in the suprachiasmatic nucleus and also indicate a small number of neurons possessing additional classes of receptor selective for either oxytocin or vasotocin. Contrary to previous reports, they also demonstrate that endogenous vasopressin tonically excites suprachiasmatic nucleus neurons. The fact that vasopressin-sensitive (but not vasopressin-insensitive) neurons show a level of basal activity correlated with time, suggests that this tone may contribute to the circadian cycle of electrical activity in the suprachiasmatic nucleus.

Action Potentials↗
PubMed1994

[Arg8]vasotocin excites neurones in the dorsal vagal complex in vitro: evidence for an action through novel class(es) of CNS receptors.

Using extracellular recordings from brainstem slices in vitro, it was demonstrated that a high proportion (38/56) of neurones in the dorsal vagal complex of dioestrus, virgin female rats exhibit an excitatory response to [Arg8]-vasotocin (AVT). Pharmacological characterization suggests that these responses cannot be entirely explained by interaction with either of the currently known classes of central receptors for oxytocin (OT) and vasopressin (V1a). Comparison of the responses with those to the OT receptor-specific agonist [Thr4,Gly7]-OT (TGOT), showed that not all neurones that responded to TGOT also responded to AVT (3/27). Furthermore, while the effects of 10(-7) M TGOT could be blocked either by the broad-spectrum antagonist d(CH2)5[d-Tyr(OEt)2,Val4,Cit8]-vasopressin or by the selective OT receptor antagonist d(CH2)5[Tyr(Me)2,Thr4,Orn8,Tyr-NH2(9)]-vasotocin, these peptides did not completely block the responses to AVT, indicating that AVT is unlikely to act through the central OT receptor. The responses to AVT and [Arg8]-vasopressin (AVP) indicated the presence of at least 2 classes of receptor with which these agonists could act. Of 42 neurones tested with both AVP and AVT, none responded to AVP in the absence of a response to AVT, while 7/42 responded to AVT without a response to AVP. This might be explained by AVP acting through only the V1 receptor, while AVT acts through both the V1 and its own novel class of receptor. This was substantiated by the fact that two OT/V1 receptor antagonists, d(CH2)5[d-Tyr(OEt)2,Val4,Cit8]-VP and d(CH2)5[Tyr(Me)2,Tyr-NH2(9)]-AVP, were unable to block completely all the responses to AVT at a dose which suppressed responses to both AVP and TGOT.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1993

Electrophysiological actions of oxytocin in the dorsal vagal complex of the female rat in vitro: changing responsiveness during the oestrous cycle and after steroid treatment.

The effect of the oxytocin-specific agonist Thr4,Gly7-oxytocin (TGOT) was tested on neurones in tissue slices of the dorsal vagal complex, obtained from virgin female rats at different stages of the oestrous cycle. The proportion of neurones excited by TGOT (0.1 microM) was independent of the day of the cycle, but both the basal activity and magnitude of response induced by TGOT were significantly reduced on the day of oestrus by comparison with dioestrus. This was due to a small but significant shift in the dose-response relationship. The magnitude of the excitation of neurones obtained from animals at proestrus did not differ significantly from either oestrus or dioestrus, but lay between the two. Ovariectomy 6 days prior to recording reduced the proportion of responsive neurones (35% vs. 69% at dioestrus), but had only a small effect on the amplitude of the averaged responses. Daily injection of 10 micrograms oestradiol benzoate had no additional effect on the proportion of responsive neurones (40%), but caused a marked suppression of the amplitude of the response at all doses (change in firing rate caused by 0.1 microM: 1.68 +/- 0.27 Hz vs. 2.69 +/- 0.39 Hz). In contrast, injections of 5 mg progesterone caused a small increase in the amplitude of the response. The data show that ovarian steroids have a marked effect on oxytocin-sensitive neurones of the dorsal vagal complex, causing dynamic changes in responsiveness over the oestrous cycle. This is discussed with respect to the effects of ovarian steroids on central oxytocin receptors and the possible involvement in regulating autonomic functions.

Animals↗
PubMed1993

Post-partum increase in oxytocin-induced excitation of neurones in the bed nuclei of the stria terminalis in vitro.

Extracellular recordings were made from neurones in the bed nuclei of the stria terminalis (BST) in brain slices from female rats on days 13-15 of pregnancy, during lactation or 5-6 days following weaning. The proportion of neurones excited by the oxytocin-specific agonist, Thr4, Gly7-oxytocin, did not change over the peri-partum period, but the magnitude of their response increased significantly during lactation. These data concur with reported changes in receptor density. It is suggested that increased oxytocin responsivity of BST neurones may subserve a regulatory function to maternal behaviour or neuroendocrine reflexes during lactation.

Animals↗
PubMed1993

Electrical activity of neurons in the ventrolateral septum and bed nuclei of the stria terminalis in suckled rats: statistical analysis gives evidence for sensitivity to oxytocin and for relation to the milk-ejection reflex.

Our previous results obtained by lesioning or stimulating the ventrolateral part of the lateral septum and the bed nuclei of the stria terminalis suggested that this area is involved in the control of milk ejection pattern in rats. The present study was undertaken with the aim of testing ventrolateral part of the lateral septum-bed nuclei of the stria terminalis neurons as a putative link of the neuronal network controlling the bursting activity of oxytocin neurons in suckled lactating rats (anaesthetized with urethane). Ventrolateral part of the lateral septum-bed nuclei of the stria terminalis neurons were recorded simultaneously with hypothalamic oxytocin neurons in either the paraventricular or supraoptic nucleus in rats with (n = 26) or without (n = 29) periodic milk ejections. Analysis of their firing pattern enabled differentiation of two subgroups: type I, characterized by numerous high frequency spikes, often grouped in clusters; and type II with very few or no high frequency clusters of spikes. The probability density function of the interspike intervals of both patterns could be modelled using a mixture of two log-normal distributions, the parameters of which differed significantly. The presence of absence of milk ejections did not influence the overall mean level of activity (2.0 +/- 0.5 and 1.9 +/- 0.4 spikes/s, respectively). However, the characteristics of the type I firing pattern were affected by the presence of the milk-ejection reflex. The average level of activity was not always constant and 16/55 ventrolateral part of the lateral septum-bed nuclei of the stria terminalis neurons displayed cyclical activity (from 0.6 +/- 0.2 to 4.0 +/- 0.5 spikes/s) both in the presence (n = 8) and absence (n = 8) of the milk-ejection reflex. In five of eight neurons recorded during milk-ejection reflex, the cycles in firing were clearly correlated with the bursting of oxytocin neurons. These five neurons exhibited the type I firing pattern. The three remaining neurons and the eight neurons recorded in the absence of milk-ejection reflex displayed the type II firing pattern. Oxytocin (1-2 ng = 0.45-0.9 mU) was injected into the third ventricle (i.c.v.) in order to examine the possible involvement of ventrolateral part of the lateral septum-bed nuclei of the stria terminalis neurons in the facilitatory effect of oxytocin on the reflex.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Oxytocin-containing pathway to the bed nuclei of the stria terminalis of the lactating rat brain: immunocytochemical and in vitro electrophysiological evidence.

Immunocytochemical staining within the forebrain of lactating rats revealed oxytocin-immunoreactive perikarya in a continuum running from the anterior parvocellular hypothalamic paraventricular nucleus through the anterior commissural nucleus and perifornical region. Beaded axons could be seen arising from these perikarya to enter the bed nuclei of the stria terminalis. In sections cut at a 45 degree angle to the parasagittal plane, much of this pathway could be maintained intact, and in vitro tissue slices prepared in this orientation were used for electrophysiological studies of oxytocinergic innervation of the bed nuclei. By extracellular recording, neurons of the bed nuclei of the stria terminalis were tested for their response to exogenous oxytocin and to stimulation of the paraventricular hypothalamus. Both short latency (3-40 ms) orthodromic excitation (26/78 neurons) and longer latency (greater than 100 ms) excitation (12/78 neurons) were observed following paraventricular hypothalamic stimulation, possibly representing mono- and polysynaptic inputs, respectively. Removal of extracellular Ca2+ blocked these orthodromic responses (n = 6). Antidromic invasion was seen in a further 11/78 neurons with characteristics of constant latency (mean = 5.9 +/- 0.7 ms), high frequency following (40-80 Hz) and persistence in Ca(2+)-free medium. When tested for the effect of oxytocin (10(-7) M), none (0/11) of the antidromically activated neurons were excited, but nine of 34 of the orthodromically excited neurons (both short and long latency) responded with a marked increase in activity. In three of eight cases, the orthodromic synaptic excitation following hypothalamic stimulation could be reversibly attenuated by the receptor antagonist [d(CH2)5,D-Tyr(OEt)2,Val4,Cit8]-vasopressin (0.5 or 2.5 x 10(-6) M), further substantiating the involvement of oxytocin. These data provide anatomical and electrophysiological evidence for an oxytocinergic innervation of the bed nuclei of the stria terminalis. This pathway is discussed in terms of possible involvement in mediating the facilitatory effect of oxytocin on the milk-ejection reflex of lactating rats which has been suggested to act through this part of the limbic system.

Animals↗