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I F Tulloch

Publications and source records attributed to I F Tulloch.

31 records · Page 2Linked to original sources
PubMed1982

The relationship between plasma concentration of valproic acid and its anticonvulsant and behavioural effects in the rat.

The relationship between the plasma concentration of valproic acid (VPA) and anticonvulsant or neurotoxic effects was studied in the rat. Anticonvulsant activity was assessed against; (1) maximal seizures induced either by electroshock or by intravenous injection of pentylenetetrazol; and (2) kindled amygdaloid epilepsy. Drug-induced neurotoxicity was determined by the rotarod test and by observation of behaviour. In the maximal seizure tests, tonic hindlimb extension was always abolished at plasma valproic acid concentrations of 225 microgram ml-1 and above. Tonic forelimb extension was not consistently blocked until the plasma drug concentration exceeded 530 microgram ml-1. In fully-kindled rats, plasma valproic acid concentrations of 300 microgram ml-1 and above markedly reduced the duration of amygdala afterdischarge activity and the intensity of behavioural seizures produced by amygdala stimulation. Analysis of the data from individual kindled rats revealed that there was a significant correlation between the estimated plasma concentration of valproic acid and the degree of seizure protection. Impairment of rotarod performance and marked ataxia occurred at plasma valproic acid concentrations above 510 microgram ml-1 and loss of righting reflex became evident at 970 microgram ml-1. From these results, it is concluded that the plasma concentration of valproic acid is closely correlated with the anticonvulsant and neurotoxic effects observed in individual rats after acute administration of sodium valproate.

Administration, Oral↗
PubMed1982

Neuropharmacological evaluation of RX 77368--a stabilised analogue of thyrotropin-releasing hormone (TRH).

L-Pyroglutamyl-L-histidyl-L-2,3-dimethylprolineamide (Pyr-His-Dmp . NH2; RX 77368) a stabilised analogue of thyrotropin-releasing hormone (TRH) has been examined for neuropharmacological effects in animal tests. The compound was more potent than either TRH or clinically established drugs in four animal tests of antidepressant potential (reserpine reversal, clonidine antagonism, tremorine reversal and learned immobility). RX 77368 also antagonised barbiturate sleeping time. Given by itself to rats the peptide produced arousal as characterised by EEG and EMG measurements and delayed the onset of sleep. The arousal induced was not accompanied by increases in locomotor activity. The profile of pharmacological activity for RX 77368 did not correspond to the profiles of tricyclic antidepressants, psychic-stimulants or analeptic drugs. The possible clinical uses for such a molecule are discussed.

Adult↗
PubMed1979

The effects of methionine- and leucine-enkephalin on spinal neurones of the cat.

Extra- and intracellular recordings were obtained from physiologically identified, spinal neurones in the 6th and 7th lumbar segments of the pentobarbitone-anaesthetized cat. Microiontophoretically applied methionine- and leucine-enkephalin reversibly inhibited the spontaneous, synaptically induced, and L-glutamate-induced activity in the majority of dorsal horn neurones studied in laminae 4, 5 and 6 of Rexed. Most of these depressant effects were antagonized by the prior microiontophoretic application of the opiate antagonist naloxone. Intracellular studies performed on dorsal horn neurones and motoneurones revealed that microiontophoretically applied methionine- and leucine-enkephalin caused no change in the resting membrane potential or the membrane resistance. Neither spike initiation nor spike overshoot were detectably altered by either enkephalin. The membrane depolarization and associated decrease in membrane resistance following microiontophoretic L-glutamate application were effectively blocked by the prior application of enkephalin. Naloxone, which by itself had no detectable effect on the membrane resistance, antagonized this effect. We propose that [enkephalinergic] cells in lamina II and III may modulate cells subserving somatosensory perception, including pain.

Animals↗
PubMed1979

Effects of substance P on neurones in the dorsal horn of the spinal cord of the cat.

The activity of single, physiologically identified neurones has been recorded both extra- and intracellularly in the 6th and 7th lumbar segments of the pentobarbitone-anaesthetized cat. In the majority of dorsal horn neurones studies (laminae 4 and 5 of Rexed) microiontophoretically applied synthetic substance P and the active fragment, substance P (4--11), were found to cause a slow and prolonged increase of the spontaneous firing rate and/or an enhancement of L-glutamate induced activity. Intracellular studies revealed that substance P caused a reversible depolarization of both dorsal horn neurones and motoneurones without a detectable alteration of the membrane resistance, antidromic action potential or postsynaptic potentials. These results are compatible with a possible role of substance P in sensory transmission in the spinal cord of the cat.

Animals↗
PubMed1978

The striatonigral fibres and the feedback control of dopamine metabolism.

It proved possible to make lesions which interrupted the striatonigral GABA-containing pathway in the rat brain without causing concomitant damage to the nigrostriatal dopamine containing system. Estimations of striatal concentrations of dopamine (DA), dihydroxyphenyl-acetic acid (DOPAC) and homovanillic acid (HVA) inducated that these lesions had no influence either on normal striatal DA turnover or on the enhancement of DA turnover induced by neuroleptics. Behavioural experiments suggested a motor output function for the striatonigral pathway.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1978

Topographical organization of the striatonigral pathway revealed by anterograde and retrograde neuroanatomical tracing techniques.

L-[4,5-3H]leucine was injected stereotaxically into various regions of the rat neostriatum. Light microscopic autoradiographic techniques were used to plot the entire efferent pathways of the neostriatum, and in particular, the projections to the substantia nigra (SN). The terminal distribution of the pathways projecting to the ipsilateral SN was predominantly restricted to the zona reticulata region. The dorsal part of the head of the striatum was found to innervate the anterior and medial portions of the zona reticulata, while the ventral area of the head projected to more posterior regions of the SN. A pathway from the tail of the striatum to the lateral and dorsal parts of SN was also demonstrated. Horseradish peroxidase injections, restricted to different areas of the SN, led to retrograde labelling of neurons in the striatum whose distribution confirmed the topographic organization of the striatonigral pathway demonstrated in the autoradiographic studies.

Animals↗