Thelma Lovick - Academia.edu (original) (raw)

Papers by Thelma Lovick

Journal of the Autonomic Nervous System, 1993

The effect on the cardiovascular response to volume load, of lesioning the paraventriculo-spinal ... more The effect on the cardiovascular response to volume load, of lesioning the paraventriculo-spinal projection to the lower thoracic cord, has been investigated in urethane-anaesthetised rats. In control animals volume loading with 4% Ficoll 70 in 165 mM NaCl at 0.6 ml/min i.v. up to 1% body weight produced a pressor response and tachycardia accompanied by a vasodilatation in the renal vascular bed. Injections of 2-4 micrograms ibotenic acid in 100-200 microliters solution were made into the paraventricular nucleus to lesion parvocellular neurones. When tested 3 days after the lesioning procedure, the renal vasodilator component of the response to volume load was abolished, although blood pressure and heart rate still rose. When the response to volume load was tested 28 days after the lesion, some degree of functional recovery appeared to have taken place. In these rats there was a weak renal vasodilation although the maximal increase in renal vascular conductance (20 +/- 13%) was still smaller than in the control animals. The efficacy of the lesioning procedure was verified by counting the number of fluorescent labelled neurones in PVN after injection of 1-2 microliters of a 1.25% solution of the retrograde marker 4,6 diamidino-2-phenyl indole (DAPI) bilaterally into the cord at T8-10. 1005 +/- 63 neurones were present in each side of PVN in non-PVN-lesioned rats whilst in lesioned animals only 444 +/- 153 cells were present. These results suggest that the paraventriculo-spinal projection to the lower thoracic cord may play an important role in sympathetically mediated changes in renal blood flow during the early phase of the response to an acute volume load.

Epilepsia, 2019

Brainstem activity, apnoea and death during seizures induced by intrahippocampal kainic acid in a... more Brainstem activity, apnoea and death during seizures induced by intrahippocampal kainic acid in anaesthetised rats.

Neural plasticity, 2009

Cyclical changes in production of neuroactive steroids during the oestrous cycle induce significa... more Cyclical changes in production of neuroactive steroids during the oestrous cycle induce significant changes in GABA(A) receptor expression in female rats. In the periaqueductal grey (PAG) matter, upregulation of alpha4beta1delta GABA(A) receptors occurs as progesterone levels fall during late dioestrus (LD) or during withdrawal from an exogenous progesterone dosing regime. The new receptors are likely to be extrasynaptically located on the GABAergic interneurone population and to mediate tonic currents. Electrophysiological studies showed that when alpha4beta1delta GABA(A) receptor expression was increased, the excitability of the output neurones in the PAG increased, due to a decrease in the level of ongoing inhibitory tone from the GABAergic interneurones. The functional consequences in terms of nociceptive processing were investigated in conscious rats. Baseline tail flick latencies were similar in all rats. However, acute exposure to mild vibration stress evoked hyperalgesia in ...

Journal of Psychopharmacology

Background and aims: We sought a robust behavioural test that evoked increased anxiety-like behav... more Background and aims: We sought a robust behavioural test that evoked increased anxiety-like behaviour during the late dioestrus phase of the oestrous cycle (similar to the premenstrual period in women) and tested whether this could be prevented by acute low-dose fluoxetine (FLX). Methods: Female Wistar rats in different stages of their cycle were exposed to four different tests of anxiety-like behaviour. Results: No oestrous cycle differences were detected in fear potentiated startle or conditioned freezing to an aversive context. In a light switch-off test where rats move from one compartment of a shuttle-box to the other to turn off an aversive light, females displayed enhanced responding in late dioestrus. During isolation restraint stress females in late dioestrus emitted three times more 22 kHz ultrasound vocalisations (USV) than at other cycle stages. Using the USV test, short-term administration of low-dose FLX (1.75 mg kg−1, i.p.) designed to blunt the sharp fall in brain al...

The Journal of comparative neurology, 2005

Premenstrual dysphoric disorder (PMDD) shows comorbidity with other psychiatric conditions such a... more Premenstrual dysphoric disorder (PMDD) shows comorbidity with other psychiatric conditions such as panic disorder (PD). The symptoms of both conditions are exacerbated during the late luteal phase of the menstrual cycle, when progesterone levels fall sharply. The present study investigated the effect of withdrawal from progesterone (PWD) on expression of alpha4, beta1, and delta GABA(A) receptor subunits in neurons within the panic circuitry of the midbrain periaqueductal gray matter (PAG) in adult female Wistar rats. Immunostaining for alpha4, beta1, and delta GABA(A) receptor subunits was present in neurons throughout the PAG in vehicle-treated animals (VEH), in rats after 24 hours withdrawal from a progesterone dosing regime (PWD, 5 mg kg(-1) i.p. twice daily for 6 days), and in animals maintained on progesterone for 7 days (HP). Compared to HP and VEH animals, which did not differ significantly from each other, the number of immunostained neurons present in the PAG of PWD rats w...

Female Wistar rats were instrumented to record bladder pressure and to stimulate the left pelvic ... more Female Wistar rats were instrumented to record bladder pressure and to stimulate the left pelvic nerve. Repeated voids were induced by continuous infusion of saline into the bladder (11.2 ml/h) via a T-piece in the line to the bladder catheter. In each animal tested (n = 6) high frequency pelvic nerve stimulation (1-3 kHz, 1-2 mA sinusoidal waveform for 60 s) applied within 2 s of the onset of a sharp rise in bladder pressure signaling an imminent void was able to inhibit micturition. Voiding was modulated in three ways: (1) Suppression of voiding (four rats, n = 13 trials). No fluid output or a very small volume of fluid expelled (<15% of the volume expected based on the mean of the previous 2 or 3 voids). Voiding suppressed for the entirety of the stimulation period (60 s) and resumed within 37 s of stopping stimulation. (2) Void deferred (four rats, n = 6 trials). The imminent void was suppressed (no fluid expelled) but a void occurred later in the stimulation period (12-44 s, mean 24.5 ± 5.2 s after the onset of the stimulation). (3) Reduction in voided volume (five rats, n = 20 trials). Voiding took place but the volume of fluid voided was 15-80% (range 21.8-77.8%, mean 45.3 ± 3.6%) of the volume expected from the mean of the preceding two or three voids. Spontaneous voiding resumed within 5 min of stopping stimulation. Stimulation during the filling phase in between voids had no effect. The experiments demonstrate that conditional high frequency stimulation of the pelvic nerve started at the onset of an imminent void can inhibit voiding. The effect was rapidly reversible and was not accompanied by any adverse behavioral side effects.

Frontiers in Physiology

Urge Urinary Incontinence: "a sudden and uncontrollable desire to void which is impossible to def... more Urge Urinary Incontinence: "a sudden and uncontrollable desire to void which is impossible to defer" is extremely common and considered the most bothersome of lower urinary tract conditions. Current treatments rely on pharmacological, neuromodulatory, and neurotoxicological approaches to manage the disorder, by reducing the excitability of the bladder muscle. However, some patients remain refractory to treatment. An alternative approach would be to temporarily suppress activity of the micturition control circuitry at the time of need i.e., urgency. In this study we investigated, in a rat model, the utility of high frequency pelvic nerve stimulation to produce a rapid onset, reversible suppression of voiding. In urethane-anesthetized rats periodic voiding was induced by continuous infusion of saline into the bladder whilst recording bladder pressure and electrical activity from the external urethral sphincter (EUS). High frequency (1-3 kHz), sinusoidal pelvic nerve stimulation initiated at the onset of the sharp rise in bladder pressure signaling an imminent void aborted the detrusor contraction. Urine output was suppressed and tone in the EUS increased. Stimulating the right or left nerve was equally effective. The effect was rapid in onset, reversible, and reproducible and evoked only minimal "off target" side effects on blood pressure, heart rate, respiration, uterine pressure, or rectal pressure. Transient contraction of abdominal wall was observed in some animals. Stimulation applied during the filling phase evoked a small, transient rise in bladder pressure and increased tonic activity in the EUS, but no urine output. Suppression of micturition persisted after section of the contralateral pelvic nerve or after ligation of the nerve distal to the electrode cuff on the ipsilateral side. We conclude that high frequency pelvic nerve stimulation initiated at the onset of an imminent void provides a potential means to control urinary continence.

Neuroscience, 2016

The aim was to investigate urodynamic parameters and functional excitability of the periaqueducta... more The aim was to investigate urodynamic parameters and functional excitability of the periaqueductal gray matter (PAG) during changes in sleep-like brain states in urethane anesthetized rats. Simultaneous recordings of detrusor pressure, external urethral sphincter (EUS) electromyogram (EMG), cortical electroencephalogram (EEG), and single-unit activity in the PAG were made during repeated voiding induced by continuous infusion of saline into the bladder. The EEG cycled between synchronized, high-amplitude slow wave activity (SWA) and desynchronized low-amplitude fast activity similar to slow wave and 'activated' sleep-like brain states. During (SWA, 0.5-1.5 Hz synchronized oscillation of the EEG waveform) voiding became more irregular than in the 'activated' brain state (2-5 Hz low-amplitude desynchronized EEG waveform) and detrusor void pressure threshold, void volume threshold and the duration of bursting activity in the external urethral sphincter EMG were raised. The spontaneous firing rate of 23/52 neurons recorded within the caudal PAG and adjacent tegmentum was linked to the EEG state, with the majority of responsive cells (92%) firing more slowly during SWA. Almost a quarter of the cells recorded (12/52) showed phasic changes in firing rate that were linked to the occurrence of voids. Inhibition (n = 6), excitation (n = 4) or excitation/inhibition (n = 2) was seen. The spontaneous firing rate of 83% of the micturition-responsive cells was sensitive to changes in EEG state. In nine of the 12 responsive cells (75%) the responses were reduced during SWA. We propose that during different sleep-like brain states changes in urodynamic properties occur which may be linked to changing excitability of the micturition circuitry in the periaqueductal gray.

The Journal of physiology, 1987

1. In cats anaesthetized with chloralose, neuronal cell bodies were excited by micro-injection of... more 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 med...

Pain, 1984

It is a common experience that during acute stress in man e.g. during battle or competitive sport... more It is a common experience that during acute stress in man e.g. during battle or competitive sport, perception of noxious sensory input is reduced. The characteristic pattern of autonomic adjustments (visceral alerting) which accompanies such fear and aggression can be evoked experimentally by electrical stimulation of the periaqueductal grey matter (PAS) (1). Stimulation in the I'AG also produces analgesia (2). Thus this

Pain, 1987

In rats anaesthetised with alphaxalone/alphadolone (Saffan), bilateral microinjections of the GAB... more In rats anaesthetised with alphaxalone/alphadolone (Saffan), bilateral microinjections of the GABA antagonist, bicuculline, into a restricted region of nucleus paragigantocelhdaris 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.

Pain, 1985

In rats anaesthetised with Saffan (Glaxovet), inhibition of the tail flick reflex evoked by elect... more In rats anaesthetised with Saffan (Glaxovet), inhibition of the tail flick reflex evoked by electrical stimulation in the dorsal periaqueductal grey matter (PAG) was accompanied by an increase in blood pressure, tachycardia, vasodilatation in hind limb muscle, an increase in respiration, pupillodilatation and widening of the palpebral fissure. Stimulation deeper in the PAG and in the tegmentum ventral to it produced analgesia but without this pattern of autonomic changes. The antinociceptive, cardiovascular and respiratory effects of PAG stimulation were abolished by bilateral lesions in the ventrolateral medulla in the area which lies ventromedial to the facial nucleus (i.e., in nucleus paragigantocellularis lateralis, RPGL). Lesions in nucleus raphe magnus (NRM), or bilateral lesions of nucleus reticularis gigantocellularis (RG) and paragigantocellularis (RPG) or a combination of a lesion in RPGL with one in NRM or the contralateral RG or RPG did not block the effects of stimulating in the dorsal PAG. These findings are discussed in relation to the role of the PAG in mediating behavioural responses to stress.

Neuroscience Letters, 1981

Neuroscience Letters, 1997

In rats anaesthetised with alphaxalone/alphadolone, electrical stimulation (10 s trains of 1 ms p... more In rats anaesthetised with alphaxalone/alphadolone, electrical stimulation (10 s trains of 1 ms pulses at 80 Hz, 40-80 mA) in the dorsolateral and lateral periaqueductal grey matter (PAG), the midbrain defence area, evoked a pressor response with tachycardia and vasodilatation in the hindlimb. Microinjection of 200 nl 0.66 mM 5HT, but not 200 nl 165 mM NaCl, at the site of stimulation attenuated the components of the PAG-evoked response by 75-98%. The effect of 5HT was significantly reduced by prior intracerebroventricular injection of 100 mg N-nitro-l-arginine methyl ester (an inhibitor of nitric oxide synthase) but not N-nitro-d-arginine methyl ester. Resting cardiovascular parameters did not change significantly following any of these manipulations. The results suggest that serotonin exerts an inhibitory modulation on the excitability of the midbrain defence area by a mechanism which involves nitric oxide.

Neuroscience Letters, 2000

The¯uorescent indicator 4,5-diamino¯uorescein (DAF-2) has been used to investigate the production... more The¯uorescent indicator 4,5-diamino¯uorescein (DAF-2) has been used to investigate the production of nitric oxide in the vicinity of intraparenchymal cerebral blood vessels. Slices of rat hippocampus 300±350 mm thick, were loaded with 5 mM DAF-2 diacetate. On exposure to light of 450±490 nm wavelength, point sources of¯uorescence, 1.8^0.2 mm in diameter (mean^SEM), were observed in close apposition to the outer surface of the vascular smooth muscle wall of 10/15 arterioles. In ®xed slices, resectioned and processed for nicotinamide adenine dinucleotide phosphate-dependent diaphorase, stained varicose ®bres were also seen in close association with the smooth muscle wall of small arterioles. These ®ndings suggest that tonic activity in perivascular nitrergic nerve ®bres lying in close proximity to intraparenchymal microvessels may be a source of dilator tone within the parenchyma.

Neuroscience Letters, 1982

Neuroscience Letters, 1989

In anaesthetised rats bilateral microinjection of 2 nmol 5-HT or the agonists 5-carboxyamidotrypt... more 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, ct-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-HTtA receptors. The possibility that there may be differences between species with respect to central 5-HT receptormediated cardiovascular effects is also discussed.