PubMed Health⌕ Search

Biomedical subjects

T A Lovick

Publications and source records attributed to T A Lovick.

At least 55 records · Page 3Linked to original sources

The rostral hypothalamus: an area for the integration of autonomic and sensory responsiveness.

1. An investigation has been made of the effects of chemical stimulation of neurons in the rostral hypothalamus on cardiovascular and respiratory parameters and on a nociceptive viscerosomatic reflex (reflex activity recorded from a lumbar spinal nerve in response to electrical stimulation of visceral afferent fibers in the splanchnic nerve) in alphaxalone/alphadolone-anesthetised rats. 2. Neurons were stimulated by microinjection of DL-homocysteic acid (DLH) at ventromedial forebrain sites between 2 mm caudal and 3 mm rostral to bregma. Any changes were monitored in viscerosomatic reflex activity and in the rate and depth of respiration, arterial blood pressure, heart rate, and hindlimb muscle blood flow. 3. Viscero-somatic reflex activity was depressed to varying degrees after injection of DLH at 20/96 sites and this was always accompanied by some form of cardiovascular change. At 8 sites inhibition of the reflex was accompanied by a cardiovascular response that included an initial pressor response (type I response) and at the other 12 sites there was an initial depressor response (type II response). Injection of DLH at a further 30 sites evoked a depressor response and no change in viscerosomatic reflex activity and at the remaining 45 sites there was no detectable change in any of the variables measured. 4. The degree of inhibition evoked from type I sites (mean 90%) was significantly greater (P < 0.001) than that evoked from type II sites (mean 58%). Type I responses were only evoked from an extremely localized region in the rostral anterior hypothalamus that corresponds to the lateral area of the anterior hypothalamus.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Excitatory 5-HT2-mediated effects on rostral ventrolateral medullary neurones in rats.

Iontophoretic application of the 5-HT2 receptor agonist alpha-methyl-5-HT excited 41 neurones in the rostral ventrolateral medulla, including a population of barosensitive cells. At high ejecting currents (greater than 2-3 x threshold) the excitation was replaced by an inhibition. The excitatory responses evoked by low doses of alpha-methyl-5-HT were reduced during iontophoretic application of ketanserin (2-5 nA) in 8/9 cells. alpha-Methyl-5-HT inhibited ongoing activity of a further 28 cells. The inhibitions were not blocked by ketanserin (n = 3). We suggest that alpha-methyl-5-HT exerts an excitatory 5-HT2-mediated effect on neurones in the rostral ventrolateral medulla.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Inhibitory modulation of the cardiovascular defence response by the ventrolateral periaqueductal grey matter in rats.

In rats anaesthetised with alphaxalone/alphadolone, electrical stimulation in the dorsal periaqueductal grey matter (PAG) evoked a pressor response with tachycardia, vasodilatation in the hindlimb and hyperpnoea: a pattern of response known as the defence reaction. Microinjection of the synaptic excitant, D,L-homocysteic acid (DLH), but not saline, into the ventrolateral PAG at the level of the decussation of the superior cerebellar peduncle (approximately 7.3-8.3 mm caudal to bregma) produced a reduction in the size of the cardiovascular components of the defence reaction evoked by electrical stimulation in the dorsal PAG. Injections of DLH made outside this region had no effect on the defence response. Injection of DLH into the "defence inhibition area" had no effect on the pressor response evoked distally in the efferent pathway for the defence reaction, by electrical stimulation in the rostral ventrolateral medulla (RVLM). Activation of neurones in a restricted portion of the caudal ventrolateral PAG appears to modulate activity in the descending pathway for the defence response evoked from the dorsal PAG. It is argued that the inhibitory interaction probably occurs at the level of synapses in the RVLM.

Animals↗

Midbrain influences on ventrolateral medullo-spinal neurones in the rat.

A study has been carried out to investigate the influence of the periaqueductal grey matter (PAG) on spinally-projecting neurones in the rostral ventrolateral medulla (RVLM) in rats anaesthetised with urethane. Microinjection of D,L-homocysteic acid was used to selectively activate nerve cell bodies in the PAG. Stimulation throughout the rostral half of the PAG and in the caudal PAG on a level with and dorsolateral to the level of the aqueduct evoked excitatory responses in 21 medullo-spinal cells in the RVLM. The neuronal excitation was associated with a rise in blood pressure. In contrast, stimulation within a restricted area of the ventrolateral PAG at the level of the dorsal raphe nucleus inhibited 10 medullo-spinal neurones in the RVLM, and produced variable changes in blood pressure. Convergence of excitatory and inhibitory influences from dorsolateral and ventrolateral stimulating sites in the PAG on to individual cells was also demonstrated. The results are discussed with respect to the role of the ventrolateral PAG in modulating the cardiovascular components of the "defence" response which is integrated by the dorsal PAG.

Animals↗

Inhibitory serotonergic effects on rostral ventrolateral medullary neurons.

In rats anaesthetised with urethane, iontophoretic application of 5-hydroxytryptamine (5-HT) and the 5-HT1A agonists buspirone, flesinoxan and 8-hydroxy-2-(di-n-propylamino)-tetralin inhibited ongoing or amino-acid-evoked activity of neurons in the rostral ventrolateral medulla (RVLM) including barosensitive cells with spinally projecting axons. More than 90% of cells tested were inhibited by these agonists. In 5/9 cells the inhibition was reduced after intravenous spiperone (0.6 mg/kg). These results suggest that the sympatho-inhibitory effects produced by microinjection of 5-HT1A agonists into the RVLM are due to a direct inhibitory action on neurons that send excitatory projections to the spinal sympathetic outflow.

Animals↗

Selective modulation of the cardiovascular response but not the antinociception evoked from the dorsal PAG, by 5-HT in the ventrolateral medulla.

In lightly ananesthetised rats, electrical stimulation in the dorsal part of the periaqueductal grey matter (dPAG) produced an increase in the latency of the tail flick response accompanied by an increase in blood pressure and heart rate. Microinjection of 40-50nmol 5-HT bilaterally into the rostral part of nucleus paragigantocellularis lateralis (PGL) at the level of the facial nucleus attenuated the cardiovascular response to stimulation of the dPAG but had no effect on the analgesia. It is suggested that cardiovascular control neurones, but not the pain control neurones in the rostral part of PGL are subject to inhibitory serotonergic modulation.

Animals↗

Systemic and regional haemodynamic responses to microinjection of 5-HT agonists in the rostral ventrolateral medulla in the rat.

In anaesthetised rats bilateral microinjection of 2 nmol 5-HT or the agonists 5-carboxyamidotryptamine (5-CT), 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) into nucleus paragigantocellularis lateralis produced a fall in blood pressure and heart rate, an increase in hindlimb vascular conductance but no significant change in renal conductance. In contrast, alpha-methyl-5-HT injected into the same region had no such effects. It is suggested that these cardiovascular effects are mediated by activation of 5-HT1A receptors. The possibility that there may be differences between species with respect to central 5-HT receptor-mediated cardiovascular effects is also discussed.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Cardiovascular responses to 5-HT in the ventrolateral medulla of the rat.

Bilateral microinjection of 5-HT into the rostral ventrolateral medulla (RVLM) produced a fall in blood pressure in anaesthetised rats. Injection of 10-20 nmol 5-HT produced a fall in mean arterial pressure of 5-55 (mean 15.7) mm Hg which lasted 1-69 (mean 25.2) min. Larger doses (up to 120 nmol) produced a similar, but longer lasting fall in pressure. The depressor response was accompanied by bradycardia but tachycardia was sometimes seen in response to injections made at the rostral tip of the RVLM. An analysis of haemodynamic changes in response to 40-50 nmol 5-HT showed the depressor response was accompanied by an increase in vascular conductance of hindlimb muscle (20-200, mean 87.2%) and a rise of 2-9 (mean 5.9)degrees C, in the surface temperature of the tail. In contrast, an increase in renal vascular conductance (8-66 (mean 19.6)%) was only evoked after injections of 5-HT into the caudal half of the RVLM whereas a decrease in conductance (14-48 (mean 24.5)%) was measured after injections of 5-HT into the rostral tip of the nucleus. The hindlimb muscle and tail vascular beds therefore appear to make a larger contribution to the fall in peripheral resistance than the renal bed.

Animals↗

Circulating atrial natriuretic factor activates vagal afferent inputs to paraventriculo-spinal neurones in the rat.

In urethane-anaesthetised, paralysed and artificially ventilated rats (300-350 g b.wt.), i.v. bolus injection of 3-5 micrograms atrial natriuretic factor (ANF) inhibited the activity of 5/8 (62.5%) antidromically identified spinally projecting neurones in the parvocellular portion of the hypothalamic paraventricular nucleus for periods of 6-40 min, mean 24 min. In contrast a much lower dose of ANF (250 ng) evoked a strong excitatory response in 37.5% of cells tested and either a weak inhibition or no effect on the remainder. Both inhibitory and excitatory effects were absent in bilaterally vagotomised animals. The results are discussed in relation to the role of circulating ANF in activating vagal afferent inputs to the paraventricular nucleus during volume loading.

Animals↗

Autonomic control of sensory responsiveness.

This paper discusses some recent evidence concerned with interactions between the sympathetic nervous system and sensory processing. There is some evidence for a direct inhibitory influence of sympathetic nerves on C-fibre somatic afferents. However, the effects are often masked by other actions which are secondary to sympathetically induced local vascular changes. In addition, in certain pathological pain states sympathetic activity does appear to enhance activity in C-fibres. Centrally induced changes in sensory responsiveness and in the pattern of ongoing sympathetic activity are fundamental components of certain behavioural states, such as aggression or sleep. Even though these changes occur in concert, there is as yet no unequivocal evidence for a common central control mechanism. The central control of the sympathetic outflow and sensory afferent input appear to be mediated independently. In contrast, increased visceral afferent input to the central nervous system, e.g. from cardiopulmonary baroreceptors, may lead to a decreased responsiveness to noxious input indirectly by enhancing centrally the activity in descending pain control pathways.

Adaptation, Physiological↗

GABA-mediated inhibition in nucleus paragigantocellularis lateralis in the cat.

In decerebrate cats electrical stimulation (10-20 ms trains, 35-450 microA, 0.1 ms pulses, 450 Hz) in nucleus tractus solitarius (NTS, medial or lateral divisions) or nucleus raphe magnus (NRM) inhibited spontaneous or amino acid-induced neuronal activity in nucleus paragigantocellularis lateralis (PGL) for 8-140 (mean 51) ms. Iontophoretically applied GABA (2-50 nA) also inhibited these cells. Iontophoretically applied bicuculline methiodide (10-80 nA) blocked the effects of GABA and reduced the duration of the inhibition evoked from NRM by greater than 50% (5/6 cells) but had no effect on the inhibition evoked from NTS (6/7 cells). The results are discussed in relation to the role of GABA in mediating inhibitory afferent input to PGL.

Action Potentials↗

Convergent afferent inputs to neurones in nucleus paragigantocellularis lateralis in the cat.

Neuronal activity was recorded in nucleus paragigantocellularis lateralis (PGL) of the cat in response to stimulation of the dorsal periaqueductal grey matter (dPAG), parabrachial nucleus (PBN) nucleus raphe magnus (NRM), and nucleus tractus solitarii (NTS). Stimulation in dPAG or PBN evoked excitatory responses whilst the prevalent response to stimulation in NRM or NTS was inhibition of neuronal activity. 45/55 (82%) of cells tested received convergent inputs from 2 or more sites of stimulation. These findings are discussed in relation to the role of PGL in cardiovascular control and descending control of noxious input.

Action Potentials↗

Electrophysiological properties of paraventriculo-spinal neurones in the rat.

In rats anaesthetized with urethane, electrical stimulation of the thoracic cord at T9-10 evoked antidromic response in neurones in the parvocellular portion of the ipsilateral paraventricular nucleus. Estimated conduction velocities in the spinally-projecting axons ranged from 0.6-5.9 m/sec. The majority (97%) of spinally projecting neurones were quiescent. Increases or decreases in the level of baroreceptor stimulation produced by intravenous injection of phenylephrine (1-5 micrograms) or sodium nitroprusside (10-15 micrograms) inhibited and excited amino acid-induced activity in 5/8 and 4/11 neurones respectively. Stimulation of vagal afferent endings by rapid bolus injection of 5-HT, to evoke the Bezold-Jarisch reflex. inhibited amino acid-induced activity in 15/18 cells. Activation of gastric vagal afferents by distension of the stomach had no effect on paraventriculo-spinal cells. It is suggested that at rest the excitability of paraventriculo-spinal neurones is depressed by a tonic inhibitory input which arises from vagal afferent fibres in the heart.

Action Potentials↗

Effects of volume loading on paraventriculo-spinal neurones in the rat.

Experiments were carried out to investigate the effects of volume loading on the activity of antidromically identified paraventriculo-spinal neurones in rats anaesthetised with urethane. Intravenous infusion of isotonic saline (1.5-4.2 ml) inhibited amino acid induced activity in 12/20 cells. Of the remainder, 4 cells were excited and 4 were unaffected by volume loading. In 4/4 neurones inhibited by volume expansion, subsequent activation of vagal afferent nerve endings by i.v. bolus injection of 5-hydroxytryptamine (25-100 micrograms) also inhibited cell firing. The onset (0.5-7 min) and duration (5-29 min) of the inhibition evoked by volume loading showed considerable variation in different animals. The inhibitory effects of volume loading were absent in bilaterally vagotomised rats (n = 4). In these preparations the activity of paraventriculo-spinal neurones was facilitated by volume loading. It is suggested that during volume loading inhibitory vagally mediated inputs and excitatory non-vagal influences converge on paraventriculo-spinal neurones.

Afferent Pathways↗

Tonic GABAergic and cholinergic influences on pain control and cardiovascular control neurones in nucleus paragigantocellularis lateralis in the rat.

In rats anaesthetised with alphaxalone/alphadolone (Saffan), bilateral microinjections of the GABA antagonist, bicuculline, into a restricted region of nucleus paragigantocellularis lateralis (PGL), ventromedial to the caudal pole of the facial nucleus, produced an increase in the latency of the tail flick response to noxious heat. The analgesia was always accompanied by a rise in mean arterial blood pressure but the time course of the cardiovascular and antinociceptive changes was different. Guanethidine (7 mg/kg i.v.) blocked the pressor response but had no effect on the magnitude or time course of the analgesia. In contrast, microinjection of physostigmine into PGL produced a pressor response but no change in the latency of the tail flick response. It is concluded that there are functionally distinct pools of neurones within PGL which respectively produce antinociception and changes in vasomotor activity. Ongoing activity in both types of neurone is regulated by a tonic inhibitory GABAergic influence. In addition, the cardiovascular neurones receive a tonic excitatory cholinergic input.

Animals↗

Differential control of cardiac and vasomotor activity by neurones in nucleus paragigantocellularis lateralis in the cat.

1. In cats anaesthetized with chloralose, neuronal cell bodies were excited by micro-injection of DL-homocysteic acid (DLH). 2. Injections made into the ventrolateral medulla in the region of nucleus paragigantocellularis lateralis (p.g.l.) produced a rise in blood pressure accompanied by either an increase or decrease in heart rate according to the precise site of the injection. The tachycardia was blocked by propranolol (0.15-0.5 mg kg-1 I.V.) whilst bradycardia was abolished by vagotomy or atropine (0.2-1.5 mg kg-1 I.V.). 3. Recordings were made of blood flow to the hind-limb, renal and mesenteric vascular beds in order to study the haemodynamic changes separately in each region. 4. Vasoconstriction was seen in the renal and mesenteric beds and either vasodilatation or vasoconstriction could be evoked in hind-limb muscle. The vasodilatation in hind-limb muscle was resistant to atropine but significantly reduced by propranolol (0.15-1.5 mg kg-1 I.V.) and therefore was probably mediated mainly by circulating adrenaline. 5. The relative contribution by each vascular bed to the rise in peripheral resistance produced by micro-injection of DLH at any one site varied according to the site of the injection and there was a degree of topographical organization within p.g.l. The neuronal pools which elicit tachycardia, renal vasoconstriction and hind-limb dilatation were located at the rostral end of the nucleus whilst those which produced vasoconstriction in the hind-limb muscle and mesenteric vascular beds were represented further caudally.

Animals↗

Projections from brainstem nuclei to the nucleus paragigantocellularis lateralis in the cat.

Afferent projections from the pons and medulla to the nucleus paragigantocellularis lateralis (PGL) have been mapped in the cat using retrograde transport of horseradish peroxidase (HRP). In the caudal medulla, the major sources of afferents were the medial and lateral divisions of the solitary nuclei complex and the contralateral trigeminal nucleus caudalis. Labelled cells were also present in the dorsal column nuclei, nucleus intercalatus and praepositus hypoglossi but this may have been due to uptake of HRP into fibres of passage. In the dorsolateral medulla and pons, neurones in the vestibular complex and in the parabrachial nucleus were labelled bilaterally. Nucleus raphe magnus and raphe obscurus were both found to send projections to the PGL and labelled cells were also present throughout the pontine and medullary reticular nuclei as well as in PGL on the side opposite to the injection of HRP. These findings are discussed in relation to the role of the PGL in cardiovascular regulation and in the control of pain.

Animals↗