Search PubMed⌕ Search

Biomedical subjects

K A Clarke

Publications and source records attributed to K A Clarke.

At least 37 records · Page 2Linked to original sources
PubMed1991

Interactions between adrenergic systems, anaesthetic and TRH analogue induced analeptic effects on VBT transmission.

Previous behavioural and electrophysiological studies have indicated an antinarcotic action of thyrotropin-releasing hormone (TRH) and its analogues in antagonizing the action of CNS depressant drugs, including baclofen and a variety of anesthetics. While beta-adrenergic receptors are implicated in the level of anaesthesia/arousal, whether the analeptic action of TRH involves adrenergic systems for its expression is uncertain. The object of the present experiments, therefore, was to examine interactions between adrenergic systems and the anti-anaesthetic effects of TRH analogue CG3703. It was found that pretreatment with the beta-block (+/-)propranolol did not abolish or reduce the ability of CG3703 to antagonize urethane-induced depression of VBT transmission. These results suggest therefore, that beta-adrenergic systems are unlikely to be involved in the anti-anaesthetic effect of the tripeptide.

Animals↗
PubMed1991

TRH analogue antagonizes anaesthetic induced depression of information transfer through the ventrobasal thalamus of the rat.

Previous studies have indicated an anti-narcotic action of TRH and its analogues. A major site of anaesthetic action is in the ventrobasal thalamus (VBT). The present experiments were performed to determine whether there was antagonism between anaesthetics and a TRH analogue on VBT transmission. It was found that the TRH analogue CG3703 reversed the depressant actions of the anaesthetics urethane, sodium pentobarbitone and sodium brietal on ventrobasal transmission. These actions were also observed at the cortical level but cuneate transmission was unaffected. These results are discussed in the context of modulation of information flow through VBT. In particular it is suggested that TRHergic input from the thalamic reticular nucleus may be an important regulator of VBT transmission.

Anesthetics↗
PubMed1990

Gait topography in rat locomotion.

Gait topography has been quantified and normative data established for free, spontaneous locomotion in rats. The normal walking pattern has been compared for male and female rats and for three rat strains. The normal walking gait was found to be symmetrical, and measures of stride width (SW) and stride length (SL) were consistent, with coefficients of variability ranging between 10 and 21%. A study of gait ontogeny found that for both male and female rats, SL increased as a linear function of body weight, whereas SW increased curvilinearly. The results indicate that repeated measures of gait topography were not subject to interference from habituation. A sex difference in gait ontogeny was observed. The developmental pattern is similar for both sexes, but males increase both SL and SW faster than females. It is proposed that gait topography may yield valuable information in activity studies.

Aging↗
PubMed1990

Antagonism of baclofen induced reduction in ventrobasal thalamic transmission by a TRH analogue.

It has been shown previously that baclofen, the GABB beta receptor agonist, reduces the excitability of ventrobasal thalamic relay neurons measured by increases in latency and decreased discharge probability, while thyrotropin releasing hormone (TRH) analogues have the opposite effects. The present experiments have shown that the excitability reducing effects of baclofen on ventrobasal transmission are antagonised by the administration of TRH analogue CG3703. These results are discussed in the context of possible GABAergic and TRHergic modulation of VBT transmission from the thalamic reticular nucleus.

Animals↗
PubMed1989

Abnormal locomotion in the rat after administration of a TRH analogue.

Previous studies have indicated that the TRH analogue CG3703 induces changes in gross measures of motor activity. The purpose of the present study was to determine whether it affected the underlying components of the locomotor cycle, stance and swing times. It has been found that while total stride time was unaffected there was an alteration in the balance between swing and dual stance times such that treated rats used longer swing times and shorter dual stance times. For both control and treated animals dual stance time increased with stride time. However, for any particular stride time, treated animals deployed longer swing times and shorter dual stance times. Possible mechanisms for these observations are discussed.

Animals↗
PubMed1986

A quantitative study of normal locomotion in the rat.

Three variables of locomotion; stride length, stride frequency and velocity have been measured in forty-eight rats. Median values were found to be 11.3 cm, 2.4 Hz and 24.2 cm/sec respectively. The results are assessed both as independent variables and in terms of their interaction. It was found that the two variables used to increase velocity (stride length and stride frequency) were not deployed equally during normal walking velocities (10-50 cm/sec). It is proposed that the study of these three readily quantifiable variables, particularly the relationships between velocity and stride frequency may be useful for the evaluation of locomotion in the assessment of neuropharmacologically active agents.

Animals↗
PubMed1986

TRH analogue affects information transfer through the ventrobasal thalamus.

Extracellular microelectrode recordings have been made from single ventrobasal thalamic neurones in rats anaesthetised with urethane. Injection of the thyrotropin releasing hormone (TRH) analogue RX77368 (2mg/kg), produced increases in spontaneous activity and decreases in the latency of response to peripheral stimulation, together with increased production of later, rhythmic discharges. These changes were maximal between 30 and 60 minutes after injection. Decreases in latency and increases in amplitude were also observed in the evoked potential recorded from the somatosensory cortex. These results are discussed in relation to previously observed effects of TRH. Since this system is important in the planning and execution of motor acts it is suggested that modification of information flow through this system could have effects on the production of motor activity.

Afferent Pathways↗
PubMed1985

Potentiation of motoneurone excitability by combined administration of 5-HT agonist and TRH analogue.

Motoneurone field potentials have been recorded from the lumbar region of the spinal cord, to antidromic stimulation of a ventral root, in rats anaesthetised with urethane. Injection of the thyrotropin releasing hormone (TRH) analogue RX77368 (1mg/kg) plus the 5-hydroxytryptamine (5-HT) receptor agonist 5-methoxy-N, N-dimethyl-tryptamine (5MeODMT 0.4mg/kg) resulted in a potentiation of the increase in amplitude and duration of response, compared to when the drugs were given singly. These results are discussed in the context of possible interactions between 5-HT and TRH systems.

Animals↗
PubMed1985

Effects of a thyrotropin releasing hormone analogue on locomotor and other motor activity in the rat.

In the present experiments, locomotion has been studied in rats after injection of TRH analogue RX77368 (10 mg/kg i.p.). The measure used was the frequency of the cyclic shifts of weight from side to side (WTF) which accompany the progress of locomotion. It therefore provides an indirect measure of stepping frequency. After injection of RX77368 there was a shift in WTFs towards higher frequencies, i.e. when the rat walked it was taking more steps per second. These results suggest that RX77368 stimulates basic motor patterns associated with locomotion. The results obtained in these experiments are compared with those obtained using different quantification methods for locomotion and there is speculation concerning the possible modes of action of RX77368 including interactions with other neurotransmitter systems.

Animals↗
PubMed1984

Locomotion in the rat after 5-hydroxy-L-tryptophan.

Previous work has shown that administration of 5HTP in amounts substantially less than those required to elicit 'serotonin syndrome' to rats pretreated witha peripheral decarboxylase inhibitor, produced increases in locomotion, measured by whole body movements. The purpose of the present work was to study the cyclic shifts of weights from side to side which underly the progress of locomotion and to see whether these change after 5HTP. From the reciprocal of the interval for one complete cycle was calculated the weight transferral frequency (WTF). The modal WTF for control and treated rats were in the ranges 1-1.49 and 2-2.49 Hz respectively, while the medians were in the ranges 2-2.49 and 2.5-2.99 Hz respectively. Testing of goodness of fit between the frequency distribution curves in control and treated animals showed significant differences. It is concluded that after 5HTP treatment, basic locomotor patterns are shifted towards higher frequencies.

5-Hydroxytryptophan↗
PubMed1984

Motoneurone excitability during antidromically evoked inhibition after administration of a thyrotrophin releasing hormone (TRH) analogue.

Acute experiments have been performed in urethane anaesthetised rats to determine the effect of a TRH analogue (RX77368) on the excitability of motoneurone pools in the lumbar region of the spinal cord to paired antidromic stimuli ( interval 10ms) delivered to the ventral root, by measuring the field potentials produced. Following the response (CR) to the first stimulus (conditioning stimulus), the response (TR) to the second stimulus (test stimulus) is reduced in size. In control experiments, the greater the amplitude of CR, the smaller TR becomes. After RX77368 injection, CR progressively increases over the initial post injection period. It would be expected therefore that during this time there would be a progressive decline in TR relative to CR. It has been shown however, that over this period there is no decline of TR relative to CR. There is speculation on a possible role of putative neuromodulators such as TRH in the maintenance of control parameters during motoneurone recruitment and/or increases in discharge frequency.

Animals↗
PubMed1983

Effect of baclofen on sensory transmission through the ventrobasal thalamic nucleus of the rat.

Previous work suggests that after administration of baclofen there is a reduction in excitatory cuneothalamic transmission, while preliminary experiments in this laboratory had shown that baclofen produces lowered level of cortical activity. Since much of the corticothalamic output is inhibitory, the consequences of possible reductions in excitatory corticopetal and inhibitory corticofugal flow into the ventrobasal thalamus required investigation. Baclofen produced increased latency and decreased probability of discharge of the short-latency discharge of single ventrobasal thalamic units to peripheral stimulation. It is suggested that these observations are compatible with a decreased excitatory cuneothalamic volley. Accompanying the decline in the early discharge was a development of later rhythmic discharges at 80-100 msec intervals, lasting up to 900 msec. This type of response is also seen in decorticate rats and has the same temporal pattern as the inhibition of the response to the second of a pair of peripheral stimuli shown in rats with an intact cerebral cortex. Since baclofen produced a decline in cortical activity (N1 wave of evoked potential, synchronisation of the ECoG), is suggested that this emergence of rhythmic activity is produced by a reduction of corticothalamic inhibition.

Animals↗
PubMed1983

Motoneurone excitability after administration of a thyrotrophin releasing hormone analogue.

Recording have been made of motoneurone field potentials at vertebral level L1 to stimulation of the ventral root, in rats anaesthetized with urethane. Injection of thyrotrophin releasing hormone (TRH) analogue RX77368 (2 mg kg-1) produced an increase in the amplitude of the field potential within 1 min of injection, reaching peak amplitude of 51-69% above control values 6-12 min after injection; the duration of the elevation was 30-65 min. Arguments are presented which show that this effect is compatible with an RX77368-induced depolarization of the motoneurone, allowing the antidromic volley to invade more cell bodies.

Action Potentials↗
PubMed1981

The effects of trimethadione on pentetrazol-induced discharges of primary muscle spindle afferents from the hind limb of the rat.

1 Recordings have been made from primary muscle spindle afferents in split dorsal root filaments of rats anaesthetized with urethane. 2 Injection of pentetrazol (PTZ, 10 mg/kg) produced elevated discharge in the afferents with intact efferents without any charge in tension or electrical activity of the muscle of origin. 3 This elevated discharge was found to contain elements of both gamma d and gamma s activation. 4 Trimethadione (100 mg/kg), itself produced a transient increase in discharge and effectively suppressed PTZ-induced discharges of the afferents for at least 2 h. 5 These results are discussed in the context of established effects on sensory and motor systems.

Afferent Pathways↗
PubMed1980

Effect of metrazol on the discharge characteristics of muscle spindle afferents from the hind limb of the rat.

The nature of altered fusimotor discharge induced by subconvulsive doses of Metrazol has been investigated in deeply anaesthetized rats. Large amplitude stretching (ramp and hold or sinusoidal) of the appropriate muscle during the course of drug action shows Metrazol to have a predominant gamma d effect on primaries, and an exclusive gamma s effect on secondaries in both plantar and dorsiflexors of ankle and toes. Small amplitude stretches revealed gamma s activity which large amplitude stretching failed to show. Experiments with convulsive doses of Metrazol show that this elevated spindle discharge precedes development of electromyographic activity. It is suggested that fusimotor activity must be considered when analysing the mechanisms of Metrazol-induced seizures in non-paralysed animals.

Animals↗
PubMed1980

Effect of catechol on the discharge of muscle spindle afferents from the hind limb of the rat.

Previous work had shown that some of the effects of catechol could be via the fusimotor system. In order to determine the extent of fusimotor involvement, recordings have been made from muscle spindle afferents in split dorsal root filaments of anaesthetised rats. Catechol failed to excite de-efferented muscle spindles therefore eliminating many possible non-fusimotor effects. Over 80% of spindle afferents with intact efferents showed increased discharge frequency 1 min after injection, this increase often following a biphasic pattern with a pronounced pre-myoclonic burst and decline followed by a more sustained period of activity during the myoclonic phase. Analysis of spontaneous twitches or twitches evoked by ipsilateral auditory stimulation showed in addition a phasic increase in discharge suggesting alpha-gamma co-activation. Both primary and secondary afferents from many muscle groups around ankle and toes had their discharge frequencies elevated. Elevation of discharge frequencies of secondaries implies increased gamma-s activity confirmed by a decrease in dynamic index. Both gamma-d and gamma-s involvement in catechol action on primaries is suggested by dynamic index measurements. Perhaps a more continuous form of testing such as sinusoidal stretches would reveal any rapid switching between activities in the two systems.

Afferent Pathways↗
PubMed1977

A pharmacological study of the spontaneous convulsive activity induced by 1,2-dihydroxybenzene (catechol) in the anaesthetized mouse.

1. The convulsive activity induced by catechol has been examined in anaesthetized mice either by determining the CD50 for the convulsions in drug-treated and control animals, or by studying the effects of various drugs on the total whole body activity. 2. The results indicate that catecholamines play no part in the mechanism of action of catechol. Drugs which alter cerebral catecholamine levels had no effect on the convulsions, nor did the alpha- and beta-adrenoceptor blocking drugs. 3. 5-Hydroxytryptamine (5-HT) could possibly be important, though results with drugs which either change brain 5-HT levels, or block 5-HT receptors were inconsistent. 4. gamma-Aminobutyric acid also appears not to be involved in the mechanism of action of catechol. 5. The results strongly suggest that catechol primarily activates a central cholinergic system, in that muscarinic and nicotinic receptor blocking drugs inhibit, and anticholinesterases potentiate the convulsions.

Acetylcholine↗