PubMed Health⌕ Search

Biomedical subjects

G W Arbuthnott

Publications and source records attributed to G W Arbuthnott.

At least 37 records · Page 2Linked to original sources
PubMed1993

Ultrastructural characteristics of enkephalin-immunoreactive boutons and their postsynaptic targets in the shell and core of the nucleus accumbens of the rat.

The present study compared the ultrastructural morphology of enkephalin-immunoreactive boutons and their postsynaptic targets in different territories of the nucleus accumbens in the rat. The synaptic bouton profiles were identified by antibodies directed against [leu5]enkephalin. Ninety-five percent of the synaptic contacts were symmetric in configuration and the remaining 5% were asymmetric. Axosomatic contacts comprised 6% of all enkephalin-immunoreactive junctions and were distributed equally in all parts of the nucleus. Most (76%) synaptic terminals contacted dendrites but they contacted proportionally fewer dendrites in the shell (71%) than in the core (78%). Moreover, enkephalin-immunoreactive synaptic boutons in the shell (19%) and caudal enkephalin-rich areas (17%) of the core contacted twice as many spines than in the remaining parts of the core (8.5%). In the core, long pallidum-like dendrites were occasionally found ensheathed in enkephalin-immunoreactive terminal boutons. We conclude that the differential arrangement of enkephalinergic contacts in the shell and core could have important functional consequences, especially when considered in relation to other known morphological and neurochemical differences between these regions.

Animals↗
PubMed1993

Substance P release from rat nucleus accumbens and striatum: an in vivo study using antibody microprobes.

Antibody-coated microprobes have provided evidence for the release of neuropeptides in localized regions of the cat spinal cord. We have applied this method to study the release of substance P (SP) from different regions of the rat brain. Anti-SP microprobes were inserted (to a depth of 8 mm) through cortex, striatum, and nucleus accumbens of halothane anaesthetised rats and remained in situ for 10 min. Microprobes (4 control and 10 post-treatment, per rat) were then incubated with 125I-SP and an autoradiographic image produced. In the region of the nucleus accumbens immunoreactive (ir) SP was detected during the first 30 min after intraperitoneal injection of d-amphetamine (4 mg/kg, P < 0.05) but not following saline (P > 0.05). During this time, no release of ir SP was seen over areas of the probes that corresponded to the striatum. At later time intervals (1-4 h) after amphetamine, binding of ir SP was detected along the whole length of the microprobes. Release of SP is thought to be due to the action of dopamine on postsynaptic cells containing this peptide. The later spread of the peptide requires further study.

Animals↗
PubMed1993

Morphological changes in the rat neostriatum after unilateral 6-hydroxydopamine injections into the nigrostriatal pathway.

Destruction of the dopamine-containing neurons in the rat substantia nigra results in morphological changes in the striatum which have been characterized at both the light and electron microscopic levels. After a unilateral 6-hydroxydopamine injection into the medial forebrain bundle, Golgi-impregnated medium-sized spiny neurons in the neostriatum ipsilateral to the injection had a lower density of spines on their dendrites than those on the contralateral side. A similar decrease in spine density was apparent from 12 days until at least 13.5 months after the lesion. A bilateral loss of spines occurred with increasing age regardless of the presence or absence of the nigrostriatal dopaminergic pathway. At the ultrastructural level, the general pattern of synaptic input to the Golgi-impregnated medium-sized spiny neurons was similar on both sides of the brain. The most obvious class of afferent boutons contacting these spiny neurons formed prominent asymmetrical synaptic specializations with the heads of the spines. The numbers of asymmetric synaptic profiles counted in random electron micrographs from the striata ipsilateral and contralateral to the lesion were not significantly different from each other. A small but significant increase in the length of asymmetric synaptic specialization profiles was, however, detected in the striata lacking a dopamine input.

Aging↗
PubMed1991

Serotonin hyperinnervation after foetal nigra or raphe transplantation in the neostriatum of adult rats.

Embryonic nigral or raphé grafts implanted in the dopamine-depleted neostriatum contain serotonergic neurones and give rise to a serotonergic hyperinnervation of the host striatum. No similar pattern of hyperinnervation is observed in rats with striatal tissue grafts, rats with nigral grafts implanted in the intact striatum, or rats with lesions alone. These observations suggest that striatal dopamine denervation induces some target-derived trophic factors that stimulate fibre growth from serotonergic as well as dopaminergic neurones.

Animals↗
PubMed1991

A light and electron microscopical study of enkephalin-immunoreactive structures in the rat neostriatum after removal of the nigrostriatal dopaminergic pathway.

The pattern of enkephalin immunoreactivity was examined in the adult rat neostriatum, at various times after unilateral removal of the nigrostriatal dopamine input by 6-hydroxydopamine injection into the medial forebrain bundle. Animals were examined 12 days, 26 days or 13 months after the lesion. Enkephalin-immunoreactive synaptic boutons (n = 1018) in the control and the dopamine-depleted neostriatum were analysed in the electron microscope. The area of enkephalin-immunoreactive synaptic bouton profiles was significantly larger in the dopamine-depleted neostriatum and this increase was maximal in rats in which the lesion had been made 26 days or 13 months previously (50% increase). The synaptic specializations of these enkephalin-immunoreactive boutons were significantly longer in the neostriatum from the injected side. Dendritic shafts were the principal postsynaptic target of these boutons (67%) but dendritic spines (18%), perikarya (6.5%) and unidentifiable small dendrites or spines (8.5%) were also contacted. The proportions of enkephalin-immunoreactive boutons on the different postsynaptic targets were not altered by the 6-hydroxydopamine lesion. The increase in enkephalin immunoreactivity observed in the dopamine-depleted neostriatum in previous studies may be explained by the increase in the size of enkephalin-immunoreactive synaptic boutons found in the present ultrastructural investigation. The observations do not rule out the possibility that there is also an increase in the number of immunoreactive synaptic boutons, due to, for example, sprouting of the existing enkephalin-containing fibres.

Animals↗
PubMed1990

Glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes are increased in the hypothalamus of androgen-insensitive testicular feminized (Tfm) mice.

In the hypothalamus of androgen-insensitive testicular feminized (Tfm) mice the normal pattern of immunohistochemical staining for glial fibrillary acidic protein (GFAP) is markedly different from normal. Along the borders of the third ventricle and in the dorsomedial and arcuate nuclei, the numbers of stained astrocytes are increased. The usual ordered array of tanycytic processes is obscured by a tangle of GFAP-stained stellate glial cells. GFAP immunostaining in other regions of the Tfm forebrain is similar to that in normal mice. These results suggest that the distribution of reactive glia in the hypothalamus may have been changed as a consequence of the genetic defect in Tfm mice.

Androgen-Insensitivity Syndrome↗
PubMed1990

Dopamine release and metabolism in the rat striatum: an analysis by 'in vivo' brain microdialysis.

Brain microdialysis studies on the mechanisms underlying dopamine release in the rat striatum provide evidence that both exocytotic and carrier-dependent processes operate in vivo. While several releasers (potassium, veratrine, amphetamine, ouabain) utilize newly synthesized stores of dopamine, tyramine is uniquely sensitive to depletion of vesicular storage by reserpine. Extracellular DOPAC is closely associated with the newly synthesized pool of dopamine and experiments with selective monoamine oxidase inhibitors suggest that DOPAC is formed mainly by MAO-A. Recent work on the two dopamine receptors suggest that release by different mechanisms may selectively activate D1 or D2 receptor subtypes.

Animals↗
PubMed1990

Brain microdialysis studies on the control of dopamine release and metabolism in vivo.

This paper studies the actions of drugs known to release dopamine from brain tissue. Most of the theoretical background to this work has been developed in experiments on slices of brain in vitro but using in vivo microdialysis we have elaborated and extended the ideas from the in vitro experiments and been able to make a direct comparison of the mechanism of action and source of dopamine released by 5 different manipulations. The mode of action of tyramine, amphetamine, veratrine, ouabain and potassium is discussed in the light of the computer model of the nerve terminal published by Justice et al. (1988). The data may lend themselves to such an interpretation, but they could be compatible with several other models.

Animals↗
PubMed1990

Electrophysiological properties of nigrothalamic neurons after 6-hydroxydopamine lesions in the rat.

Extracellular recordings were made from electrophysiologically identified nigrothalamic cells in the substantia nigra pars reticulata of anaesthetized rats. The firing rate, firing pattern and responses to striatal stimulation were investigated in normal animals and in animals in which dopamine concentration in the ipsilateral striatum was reduced by more than 90%. At relatively short times after the lesion (less than 10 days) the mean firing rate of the spontaneously active cells in the population was significantly reduced and there was an increase in the occurrence of bursting activity. There was also a significant increase in the number of silent cells, located by antidromic stimulation from the thalamus. In spite of this reduction in mean firing rate the responses of neurons to stimulation of either the ipsilateral striatum or ventromedial thalamus was much larger in cells from lesioned animals. At longer times after the lesion (more than six months) the average firing rate of the neurons had returned to normal but there was still a prevalence of bursting activity and a consequent reduction in mean inter-spike intervals. There was little evidence of the previous hyper-responsiveness to thalamic stimulation but the responsiveness to striatal stimulation was still significantly elevated.

Animals↗
PubMed1990

Distribution and synaptic contacts of the cortical terminals arising from neurons in the rat ventromedial thalamic nucleus.

Injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin within the ventromedial thalamic nucleus resulted in many filled fibres in the frontal areas of rat cerebral cortex. The fibres were restricted to the upper part of layer I except in a small area of motor cortex where terminals were also found in deeper layers. Terminals were also seen in the striatum, in parts of the mesencephalic reticular formation and occasionally in the contralateral ventromedial nucleus. There is some topographical order in the projection with medial and dorsal areas well represented in medial cortex while lateral parts of ventromedial nucleus are more directly related to the cortical area that receives the ventrolateral thalamic nucleus projection. Electron microscopic examination showed the terminals in layer I of cortex making synaptic contact with dendritic spines and small dendritic profiles that showed a very dense postsynaptic specialization. Neurons in the ventromedial nucleus could be antidromically driven from electrode positions along strips of cortex which could not be easily related to any known organizational pattern in the cortex. Thalamic neurons responding antidromically to only one stimulation site were more common when the stimulation was within motor cortical areas, suggesting that in this region a more restricted pattern of termination is the rule.

Animals↗
PubMed1990

Effects of selective monoamine oxidase inhibitors on the in vivo release and metabolism of dopamine in the rat striatum.

Brain microdialysis was used to examine the in vivo efflux and metabolism of dopamine (DA) in the rat striatum following monoamine oxidase (MAO) inhibition. Relevant catecholamines and indoleamines were quantified by HPLC coupled with a electrochemical detection system. The MAO-B inhibitor selegiline only affected DA deamination at a dose shown to inhibit partially type A MAO. Alterations in DA and metabolite efflux were not observed when using the MAO-B-selective dose of 1 mg/kg of selegiline. At 10 mg/kg, selegiline reduced the efflux of DA metabolites to approximately 70% of basal values without affecting DA efflux. K(+)- and veratrine-stimulated DA efflux was not affected by selegiline. Experiments using amphetamine and the DA uptake inhibitor nomifensine demonstrated that the effect of selegiline on DA metabolism was unlikely to be mediated either by inhibition of DA uptake or by an indirect effect of its metabolite amphetamine. The possibility that the effect of selegiline is mediated via a nonspecific inhibition of MAO is discussed. In contrast, the MAO-A inhibitor clorgyline inhibited basal DA metabolism and increased basal and depolarisation-induced DA efflux. A 1 mg/kg dose of clorgyline reduced basal DA metabolite efflux (40-60% of control values) without affecting DA efflux. At 10 mg/kg of clorgyline, DA efflux increased to 253 +/- 19% of basal values, whereas efflux of DA metabolites was reduced to between 15 and 26% of control values. The release of DA induced by K+ and veratrine was not affected by 1 mg/kg of clorgyline but was increased by approximately 200% following pretreatment with 10 mg/kg of clorgyline. The nonselective MAO inhibitor pargyline caused similar but more pronounced alterations in these parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamine↗
PubMed1990

In vivo mechanisms underlying dopamine release from rat nigrostriatal terminals: I. Studies using veratrine and ouabain.

The in vivo mechanisms underlying the dopamine (DA)-releasing actions of veratrine and ouabain in the striatum of halothane-anaesthetised rats have been investigated using brain microdialysis. Relevant catecholamines and indoleamines were separated and quantified using HPLC combined with an electrochemical detection system. Veratrine (10 micrograms/ml-1 mg/ml) and ouabain (10 microM-1 mM) were added to the medium perfusing the dialysis probes. Both compounds increased dialysate DA content in a dose-related manner. Dialysate levels of the DA metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid and the serotonin metabolite 5-hydroxyindoleacetic acid were reduced by both veratrine and ouabain. Veratrine-induced DA efflux was maximal in the first 20-min sample collected after drug infusion began, whereas the maximal effect of ouabain was not observed until 20-40 min after administration began. Veratrine-induced DA efflux was unaffected by systemic injection of the DA uptake inhibitor nomifensine but was inhibited by either coperfusion of tetrodotoxin (TTX) or removal of calcium from the perfusing buffer. These data suggest that veratrine induces release of DA via a carrier-independent mechanism, perhaps involving an exocytotic release process. In contrast, ouabain-induced DA release was reduced by nomifensine but was inhibited to a lesser degree by calcium depletion and TTX. Detailed analyses of these data suggest that although ouabain initially induces release of DA via a carrier-dependent mechanism, an exocytotic process may also be involved. The finding that ouabain-induced DA efflux exhibits a degree of TTX and calcium sensitivity suggests that membrane depolarisation caused by Na+,K(+)-ATPase blockade opens voltage-gated sodium channels and initiates an exocytotic release of DA. The intracellular pools of DA involved in the release of DA induced by veratrine and ouabain were also examined. Depletion of vesicular pools of DA by pretreatment with reserpine reduced the amount of DA release induced by both agents, although this effect was only significant in the case of veratrine. However, in reserpinised animals the residual amount of DA release induced by veratrine was inhibited by nomifensine, a result suggesting that DA may be released via a carrier-dependent process in the absence of vesicular DA. Newly synthesised pools of DA were also depleted by pretreatment with the DA synthesis inhibitor alpha-methyl-p-tyrosine. Under these conditions, both veratrine- and ouabain-induced DA efflux was reduced.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

In vivo mechanisms underlying dopamine release from rat nigrostriatal terminals: II. Studies using potassium and tyramine.

The brain microdialysis technique has been used to examine the in vivo effects of potassium and tyramine on dopamine (DA) release and metabolism in the striatum of halothane-anaesthetised rats. Increasing the concentration of potassium perfusing the dialysis probe (30-120 mM) induced a dose-related efflux of DA. A dose-related release of DA was also observed following addition of tyramine (1-100 microM) to the perfusing buffer. High concentrations of potassium were found to reduce the dialysate content of the DA metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid and the serotonin metabolite 5-hydroxyindoleacetic acid. No such effect was observed even when using the highest concentration of tyramine tested. Potassium-evoked DA release was facilitated by pretreatment with the DA uptake inhibitor nomifensine, was inhibited by depletion of extracellular calcium, and was not significantly affected by tetrodotoxin (TTX). The effect of tyramine on DA efflux was inhibited by nomifensine and was insensitive to both TTX and calcium depletion. These data suggest that potassium and tyramine induce release of DA via different mechanisms. Potassium-induced DA release involves a carrier-independent process and may utilise an exocytotic release mechanism. On the other hand, tyramine-induced DA release would appear to involve a carrier-dependent process. Depletion of vesicular stores of DA by pretreatment with reserpine did not significantly affect potassium-induced DA release, whereas a marked inhibition of the effects of tyramine was noted. However, in reserpinised animals the potassium-induced release of DA was inhibited by nomifensine, a result suggesting that a carrier-dependent release mechanism operates in the absence of vesicular DA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Spine density on neostriatal neurones changes with 6-hydroxydopamine lesions and with age.

Golgi-impregnated medium-size spiny neurones were studied in the rat neostriatum at various times after a unilateral 6-hydroxydopamine lesion of the medial forebrain bundle. At both short (12-26 days) and long (7-12 months) survival times, the density of spines was significantly lower (13%) on neostriatal neurones ipsilateral to the 6-hydroxydopamine injection. At longer times the density of spines was lower on neurones both ipsilateral and contralateral to the lesion when compared to neurones taken from short-term animals (23%).

Aging↗