Search PubMed⌕ Search

Biomedical subjects

C J Pycock

Publications and source records attributed to C J Pycock.

68 records · Page 4Linked to original sources
PubMed1976

Possible GABA-mediated control of dopamine-dependent behavioural effects from the nucleus accumbens of the rat.

The effect of elevating GABA levels in the region of the nucleus accumbens on various dopamine-dependent behaviours in the rat has been studied. The GABA-transaminase inhibitor, ethanolamine O-sulphate (EOS) was injected bilaterally (through a needle angled at 45 degrees) into the nucleus accumbens. This resulted in a 4-5 fold increase in the GABA concentrations in the mesolimbic areas on day 1, a 2-fold increase on day 3, and a return to normal by day 7. Moderate increases in striatal and cortical GABA levels were also seen on days 1 and 3. At all times animals exhibited normal spontaneous activity and exploratory behaviour in a hold-board apparatus. However, on day 1, when mesolimbic GABA levels were maximal, a low dose of systematically administered amphetamine (0.5 mg/kg) did not induce the increased locomotor activity seen in a control group of animals. Similarly on day 1, the direct injection of dopamine into the nucleus accumbens of rats previously injected with EOS did not evoke the usual hyperactivity response. This response returned to normal on day 7. Apomorphine-induced stereotyped behaviour patterns observed on days 1 and 2 did not significantly differ in those rats previously injected with EOS with animals of a control group. A possible GABA-mediated control of dopaminergic mechanisms in the nucleus accumbens is suggested, and the possible site of interaction discussed.

4-Aminobutyrate Transaminase↗
PubMed1976

Effects of drugs acting on cerebral 5-hydroxytryptamine mechanisms on dopamine-dependent turning behaviour in mice.

1. The effects of drugs acting on cerebral 5-hydroxytryptaminergic mechanisms on drug-induced turning behaviour in mice with unilateral destruction of nigro-striatal dopaminergic nerve terminals have been studied. 2. Administration of L-tryptophan (400 mg/kg) or 5-hydroxytryptophan (200 mg/kg) increased brain 5-hydroxytryptamine and decreased the turning induced by both apomorphine (2 mg/kg) and amphetamine (5 mg/kg). 3. Parachlorophenylalanine (3 X 500 mg/kg) decreased brain 5-hydroxytryptamine and increased both apomorphine and amphetamine-induced circling behaviour. 4. Varying the protein content of dietary intake significantly altered brain 5-hydroxytryptamine and tryptophan levels, spontaneous locomotor activity and amphetamine-induced circling behaviour in these mice. 5. Systemic administration of methysergide (0.5-4 mg/kg), lysergic acid diethylamide (0.025-0.2 mg/kg), cyproheptadine (2.5-20 mg/kg) or clomipramine (0.6-20 mg/kg) produced no consistent effect on drug-induced turning behaviour. 6. The results suggest that circling behaviour due to striatal dopamine receptor stimulation is depressed by an elevation of brain 5-hydroxytryptamine and enhanced by a reduction in brain 5-hydroxytryptamine. 7. The possible physiological relationship between dopamine and 5-hydroxytryptamine neurones in the basal ganglia is discussed.

Amphetamines↗
PubMed1975

Circling behaviour produced by unilateral lesions in the region of the locus coeruleus in rats.

Rats with unilateral lesions in the region of the locus coeruleus circled tightly to the opposite side when given apomorphine or amphetamine. This turning behaviour was transient and disappeared within some 30 days after surgery. It was seen most obviously in animals with severe unilateral destruction of the locus coeruleus, which caused on average a 55% reduction in the level of noradrenaline in the ipsilateral cerebral cortex. It was not marked in animals with partial unilateral lesions of the locus coeruleus, which caused only an average fall in cortical noradrenaline of 22%. It was not seen in sham operated animals or animals in which lesions were placed into adjacent structures such as the cerebellum above, superior cerebellar peduncle laterally, and brain stem ventrally. A clue to the mechanism of this phenomenon may lie in the observation that dopamine in the ipsilateral striatum was increased 5 days after operation, when circling occurred, but had returned to normal by 30 days when circling had ceased. It is suggested that the lesion causes a reduction in impulse traffic in the ipsilateral nigrostriatal pathway, and that circling is due to preferential stimulation of the ipsilateral striatal dopamine receptors by both drugs; apomorphine directly, amphetamine by release of endogenous dopamine.

Amphetamine↗
PubMed1974

The effect of bretylium on endogenous and newly-synthesized noradrenaline in the microsomal fraction of rat heart.

Bretylium reduced the content of endogenous and newly-synthesized noradrenaline (NA) and also reduced the specific activity of NA in the microsomal fraction of rat heart. Bretylium also decreased the endogenous NA content of the microsomal subfraction which equilibrated in the 0.7 M sucrose region of a density gradient; it was without effect on the NA content of other subfractions.

Animals↗
PubMed1973

The effects of bretylium on the subcellular distribution of noradrenaline and on adrenergic nerve function in rat heart.

1. The effects of bretylium were investigated on the content and subcellular distribution of noradrenaline in the rat heart and on the response to stimulation of the sympathetic nerves supplying the heart.2. In most experiments bretylium produced no change in the total noradrenaline content of the heart but significant changes were produced in the subcellular distribution of noradrenaline.3. Treatment with amphetamine both prevented and antagonized the bretylium-induced adrenergic neurone blockade and most of the accompanying changes in the subcellular distribution of noradrenaline.4. There was a temporal correlation between the bretylium-induced depletion of noradrenaline from the microsomal (P(2)) fraction and adrenergic neurone blockade.5. The onset of adrenergic neurone blockade was also accompanied by an elevation of the noradrenaline content in the low-speed coarse (P(1A)) fraction and in the mitochondrial (P(1B)) fraction; this elevation was prevented by pretreatment with alpha-methyl-p-tyrosine.6. It is concluded that although the elevation of the noradrenaline content of the P(1A) and P(1B) fractions and a depletion of amine from the P(2) fraction are associated with the onset of adrenergic neurone blockade only the depletion from the P(2) fraction is required for its maintenance. This conclusion supports the hypothesis that only a small portion of the noradrenaline content of an adrenergically-innervated organ is associated with the release of transmitter, for when this small ;store' is depleted, by agents like bretylium, the nerves fail to function.

Amphetamine↗
PubMedDate not supplied

Central deopaminergic receptor supersensitivity and its relevance to Parkinson's disease.

The degeneration of the substantia nigra that characterises Parkinson's disease may cause an alteration in sensitivity of striatal dopamine receptors. The development of denervation supersensitivity has been held to be responsible for some of the effects of chronic levodopa therapy. The rotating rodent is an animal model commonly used to study the phenomenon of striatal dopamine receptor supersensitivity, and to investigate drugs which may prove to be beneficial in the treatment of Parkinson's disease. We have investigated as to whether long-term oral administration of levodopa to mice with unilateral destruction of striatal dopaminergic nerve terminals influences dopaminergic receptor denervation supersensitivity as judged by the circling response following systemically administered levodopa. It does not do so and the relevance of these findings to the treatment of Parkinson's disease is discussed.

Animals↗
PubMedDate not supplied

Retinal neurotransmission.

The mammalian retina is classically divided into ten layers which contain the neuronal elements identified as photoreceptors, horizontal cells, bipolar cells, amacrine cells and ganglion cells. Using various neuroscientific techniques possible neurotransmitter substances have been assigned to each of these cell types. Thus the localization of transmitter synthesizing enzymes and storage vesicles, the demonstration of release of transmitter in response to specific stimuli, the observation of post-synaptic events mimicked or blocked by the iontophoretic application of exogenous transmitter/agonist or antagonist drug respectively, and the identification of efficient transmitter inactivation mechanisms synaptically add evidence for the association of certain proposed transmitter substances with specific neuronal elements. The evidence for the proposal that the excitatory amino acids glutamate and aspartate are transmitters of photoreceptors, that gamma-aminobutyric acid (GABA) is the inhibitory transmitter of horizontal and amacrine cells, that acetylcholine is associated with the functioning of bipolar cells, and that taurine, glycine and dopamine may all also play neurotransmitter or neuromodulatory roles at amacrine cell synapses is discussed.

Acetylcholine↗
PubMedDate not supplied

Management of heart disease in the elderly in the Plymouth Health District.

In the light of a report from the Royal College of Physicians, the management of heart disease in the elderly (> 70 years) was studied in the Plymouth Health District in 1992. A survey of general practitioners was undertaken to assess how they would handle particular aspects of heart disease in their elderly patients. The admissions of older patients to the coronary care unit following an acute myocardial infarction and their outcome were detailed. The numbers of non-invasive cardiological investigations undertaken in the elderly were monitored, as were the referral rates to a cardiology outpatient clinic. The overall conclusion is that physicians and general practitioners alike view coronary artery disease as a medical condition with little consideration of the surgical option, despite good evidence that elderly patients often do very well following coronary artery bypass grafting. Future resource planning should address the problem of an overburdened cardiac surgery service.

Aged↗