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C J Pycock

Publications and source records attributed to C J Pycock.

At least 19 recordsLinked to original sources
PubMed1979

Specific stimulating effect of glycine on 3H-dopamine efflux from substantia nigra slices of the rat.

The effect of glycine was studied on the efflux of tritium-labelled dopamine, 5-HT and GABA from small slices of rat substantia nigra in vitro. A depolarising stimulus (50 mM KCl) stimulated the efflux of 3H-5HT, 3H-dopamine and 3H-GABA in a calcium-dependent fashion. Glycine (50 and 100 micromoles) stimulated the spontaneous efflux of 3H-dopamine but not that of 3H-5HT or 3H-GABA. Taurine, GABA and beta-alanine, all at 100 micromoles, had no effect on release of radioactivity after prelabelling nigral slices with 3H-dopamine. In keeping with a transmitter role for glycine at this site, 3H-glycine was taken up by small slices of rat substantia nigra by both high affinity (Km = 2.4 micromoles) and low affinity systems (Km = 5.96 mM). However 50 mM KCl was without effect on the efflux of radioactivity from nigral slices prelabelled with 3H-glycine.

Alanine↗
PubMed1979

The effects of 5,7-dihydroxytryptamine lesions of extrapyramidal and mesolimbic sites on spontaneous motor behaviour, and amphetamine-induced stereotypy.

5,7-Dihydroxytryptamine lesions of the nucleus accumbens septi, or substantia nigra, resulted in a twofold increase in spontaneous locomotor activity. Striatal 5HT depletion also raised basal activity levels, as well as increasing rearing behaviour in an open field. The sterotyped responses to all doses of amphetamine tested (2.5--10 mg/kg, i.p.) were enhanced by lesions of the nucleus accumbens or substantia nigra. Striatal lesions only affected the response to the lowest dose of amphetamine. Lesions of the tuberculum olfactorium were without effect on spontaneous or amphetamine induced responses. The results support the concept of a modulatory 5HT influence on nigro-striatal function, and suggest that 5HT in the nucleus accumbens has an antagonistic role with respect to dopamine function in this site.

5,7-Dihydroxytryptamine↗
PubMed1979

Dopamine-dependent hyperactivity in the rat following manipulation of GABA mechanisms in the region of the nucleus accumbens.

The effect of manipulation of GABA mechanisms in the region of the nucleus accumbens on dopamine-dependent locomotor hyperactivity in the rat has been studied. Two models of hyperactivity were used: (1) the injection of dopamine into the region of the nucleus accumbens in nialamide-pretreated animals and (2) the systemic administration of d-amphetamine. Both GABA and the GABA agonist 3-aminopropane sulphonic acid (3-APS) depressed hyperactivity in a dose-related manner. High concentrations of GABA (greater than 100 micrograms) were required to produce a significant effect and the response was short-lived possibly reflecting the efficient GABA inactivating mechanisms. 3-APS proved to be approximately 10 times more potent as compared to GABA in the dopamine-accumbens hyperactivity model. Conversely GABA receptor antagonism with low doses of either picrotoxin or bicuculline enhanced the mild locomotor response induced by a low dose of dopamine injected into the nucleus accumbens. However such results were difficult to evaluate fairly as higher doses of the GABA antagonists resulted in varying degrees of generalized seizures. Blockade of GABA uptake systems with cis-1, 3-aminocyclohexane carboxylic acid (ACHC), nipecotic acid or beta-alanine within the region of the nucleus accumbens produced dose-related depression of dopamine-dependent hyperactivity in both models. GABA uptake blockade (nipecotic acid) significantly enhanced the GABA-mediated depression of hyperactivity induced by bilateral injection of dopamine into the nucleus accumbens. The results demonstrate an inhibitory action of GABA and drugs facilitating GABA-ergic transmission on dopamine-dependent hyperactivity in the rat. Although open to criticisms of not being able to distinguish between true GABA effects and the results of non-specific neuronal depression the hyperactivity model underlines the potency of the GABA uptake blocking compounds and their possible potential for future clinical use.

Amino Acids↗
PubMed1979

Potentiation of haloperidol-induced catalepsy by dopamine agonists: possible involvement of central 5-hydroxytryptamine.

Apomorphine (0.12--2 mg/kg, SC) and d-amphetamine (1--8 mg/kg, IP) were each able, at certain doses, to potentiate the cataleptic state produced by the neuroleptic agent, haloperidol (1 mg/kg, IP). In subsequent biochemical experiments, in which the effects of combinations of apomorphine or d-amphetamine and haloperidol on brain monoamine levels were studied, this behavioural observation was seen to be related to an enhanced utilisation of 5-hydroxytryptamine (5-HT) in certain brain regions. The results suggest not only the possible involvement of 5-HT in the production of catalepsy, but also that the effects of these 'classical' dopamine agonists on other central transmitter systems should be considered when interpreting their various behavioural responses.

Animals↗
PubMed1979

Thyrotrophin releasing hormone stimulates release of [3H]-dopamine from slices of rat nucleus accumbens in vitro.

Thyrotrophin releasing hormone (TRH) (25 to 100 microM) was found to stimulate the efflux of [3Hu-dopamine from small slices of rat nucleus accumbens, but not from similar slices of rat caudate nucleus. Uptake inhibition was not responsible for this action, since at 10 and 50 microM TRH had no effect on the ability of small slices of nucleus accumbens to accumulate radioactivity when incubated with 10(-7) M [3H]-dopamine. In addition the hormone had no effect on basal or dopamine-stimulated adenylate cyclase, nor did it displace [3H]-spiperone binding, in membrane preparations from nucleus accumbens.

Adenylyl Cyclases↗
PubMed1979

Role of taurine as a possible transmitter in the thermoregulatory pathways of the rat.

Taurine (10 and 20 micrograms) injected unilaterally into the lateral ventricle of rats caused an increase in core temperature. Bilateral injection of taurine 2.5 and 5 micrograms into the preoptic region of the anterior hypothalamus induced a dose-related hyperthermia: higher doses (10 micrograms) caused hypothermia. Intrahypothalamically taurine-induced hyperthermia was blocked by prior injection of strychnine hydrochloride (5 and 15 micrograms); doses which alone had no effect on core temperature. Of the other inhibitory amino acids injected intrahypothalamically hypotaurine also induced a hyperthermia. GABA (10 micrograms) caused hypothermia; glycine (10 micrograms) had no effect. Potassium (50 mM) stimulated release of radioactivity from superfused slices of anterior hypothalamus prelabelled with [3H]taurine in a calcium-dependent manner. A high affinity uptake mechanism with a Km of 8.5 microM was demonstrated with [3H]taurine into slices of anterior hypothalamus. Taurine may have a neurotransmitter role in the anterior hypothalamus but whether the body temperature effects represent physiological or pharmacological events remains to be established.

Animals↗
PubMed1978

The rotating rodent: a two component system?

The hypothesis that the rotating rat requires both nigro-striatal and mesolimbic dopaminergic components for activity has been tested. 6-Hydroxydopamine lesions were induced unilaterally in either or both the ascending nigrostriatal and mesolimbic dopamine pathway. In one group of rats the nucleus accumbens was destroyed bilaterally with electrolesions. Circling behaviour was only recorded when there was both an imbalance in striatal dopamine concentrations concomitant with stimulation of the limbic dopamine regions. Lesions of the mesolimbic dopamine pathway resulted in changes in drug-induced motor activity but postural asymmetry or circling behaviour was not observed. The results support the hypothesis that the rotating rodent requires two functional dopamine components: striatal dopamine imbalance causing a postural asymmetry and stimulation of mesolimbic dopamine systems providing a locomotor component. The relevance of these components in this animal model is discussed with reference to dopaminergic agonist and antagonist drugs.

Animals↗
PubMed1978

A study of the sites of interaction between dopamine and 5-hydroxytryptamine for the production of fluphenazine-induced catalepsy.

The effect of reducing 5-hydroxytryptamine (5-HT) concentration within various areas of the central dopamine (DA) system on catalepsy has been investigated. The neurotoxin 5,7-dihydroxytryptamine was used to selectively deplete 5-HT in the striatum, nucleus accumbens septi, tuberculum olfactorium or substantia nigra. Localised depletion of 5-HT within the nucleus accumbens septi and substantia nigra reduced the cataleptic effects of the neuroleptic agent fluphenazine, while lesions of the striatum or tuberculum olfactorium were without effect. Each injection of neurotoxin resulted in a 38--47% depletion of 5-HT in the target site: DA levels were not significantly altered. The results suggest that varied dopamine/5-hydroxytryptamine interactions within the nucleus accumbens may contribute to the action of the neuroleptic. The reduction of fluphenazine-induced catalepsy produced by 5-HT depletion within the substantia nigra supports the concept of a controlling influence of 5-HT on nigro-striatal DA function.

Animals↗