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G W Arbuthnott

Publications and source records attributed to G W Arbuthnott.

At least 55 records · Page 3Linked to original sources
PubMed1989

Electrophysiological and anatomical observations concerning the pallidostriatal pathway in the rat.

Anatomical studies in several species have demonstrated a pallidostriatal pathway. We employed electrophysiological and anatomical methods to distinguish the neurones of this pathway from the two pallidocortical groups reported in the rat. Injection of fluorescent retrograde tracers, combined with immunohistochemistry for choline acetyltransferase, provided anatomical evidence of the distinction between neurones of the cholinergic pallidocortical projection and pallidal cells retrogradely labelled from the striatum. Extracellular recordings made in the globus pallidus of halothane-anaesthetised rats provided an electrophysiological description of the pallidostriatal pathway. In some animals neurones of this pathway were distinguished from pallidocortical neurones as a stimulating electrode, situated in the crus cerebri, permitted identification of neurones which projected through this region as well as to the striatum. Neither pallidocortical pathway is reported to have descending axons travelling in the crus cerebri at this point. A preliminary electrophysiological study was carried out in rats in which the dopamine-containing cells of substantia nigra had been destroyed by injections of 6-hydroxydopamine at least 6 months prior to the recording. In the globus pallidus on the lesioned side the mean firing rate of neurones was increased compared with controls. No specific change in firing pattern was noted but the neurones were more responsive to striatal stimulation suggesting that long-term dopamine denervation alters the sensitivity of neurones of globus pallidus.

Action Potentials↗
PubMed1988

An afterhyperpolarization recorded in striatal cells 'in vitro': effect of dopamine administration.

Parahorizontal slices of the neostriatum from young adult male rats were maintained at the fluid interface of a perfusion chamber. Intracellular recordings were made with potassium acetate filled micropipettes. The mean resting membrane potential of the neurones was -84 mV and all produced action potentials which overshot 0 mV. All the cells were silent at resting membrane potentials and only fired in response to depolarizing pulses delivered through the intracellular electrode. When long pulses were applied, the firing rate within the train of action potentials evoked was slower at the end of the pulse. In a very few cells at resting membrane potential, but in all cells depolarised from a holding potential of -65 mV, the resulting train of action potentials was followed by a slow hyperpolarizing potential. The potential observed was smaller in amplitude than the afterhyperpolarization seen in hippocampal pyramidal cells in vitro, but its voltage sensitivity was similar. Iontophoresis of dopamine (DA) close to the recording pipette resulted in two distinct actions. Firstly, DA reduced the number of action potentials following a short pulse, by increasing the threshold for spike initiation. Secondly, it also inhibited the hyperpolarizing potential which followed trains of action potentials even when allowance was made for the increased firing threshold. The inhibition of this hyperpolarization was accompanied by an increase in the number of spikes per pulse. Whether these two actions of DA are mediated by a single receptor/membrane action is unclear. Nevertheless, they may help to reconcile the contradictory literature regarding the action of DA upon extra-cellular responses in striatal cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1988

Amphetamine-induced dopamine release in the rat striatum: an in vivo microdialysis study.

The effects of a number of biochemical and pharmacological manipulations on amphetamine (AMPH)-induced alterations in dopamine (DA) release and metabolism were examined in the rat striatum using the in vivo brain microdialysis method. Basal striatal dialysate concentrations were: DA, 7 nM; dihydroxyphenylacetic acid (DOPAC), 850 nM; homovanillic acid (HVA), 500 nM; 5-hydroxyindoleacetic acid (5-HIAA), 300 nM; and 3-methoxytyramine (3-MT), 3 nM. Intraperitoneal injection of AMPH (4 mg/kg) induced a substantial increase in DA efflux, which attained its maximum response 20-40 min after drug injection. On the other hand, DOPAC and HVA efflux declined following AMPH. The DA response, but not those of DOPAC and HVA, was dose dependent within the range of AMPH tested (2-16 mg/kg). High doses of AMPH (greater than 8 mg/kg) also decreased 5-HIAA and increased 3-MT efflux. Depletion of vesicular stores of DA using reserpine did not affect significantly AMPH-induced dopamine efflux. In contrast, prior inhibition of catecholamine synthesis, using alpha-methyl-p-tyrosine, proved to be an effective inhibitor of AMPH-evoked DA release (less than 35% of control). Moreover, the DA releasing action of AMPH was facilitated in pargyline-pretreated animals (220% of control). These data suggest that AMPH releases preferentially a newly synthesised pool of DA. Nomifensine, a DA uptake inhibitor, was an effective inhibitor of AMPH-induced DA efflux (18% of control). On the other hand, this action of AMPH was facilitated by veratrine and ouabain (200-210% of control). These results suggest that the membrane DA carrier may be involved in the actions of AMPH on DA efflux.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Electrophysiological demonstration of host cortical inputs to striatal grafts.

Adult rats received a unilateral injection of ibotenic acid into the striatum, resulting in an extensive loss of intrinsic striatal neurones. Transplanted striatal cells from embryonic day 14 rat foetuses grew well in the damaged tissue and approximately 6 months later brain slices were cut in such a way as to include the grafts and nearby cortical tissue. Electrophysiological recordings from the grafts showed typical extracellular responses to stimulation of the subcortical white matter. Thresholds and latencies for responses were similar in grafted and control striatum. The grafted cells, however, appeared to be subject to less collateral inhibitory control than normal striatal neurones. The similarities between the responses of grafted neurones and those in normal striatum suggest that corticostriatal connections reform after transplantation, which may be an important component in the behavioural recovery observed in similar animals.

Animals↗
PubMed1985

Separation of the motor consequences from other actions of unilateral 6-hydroxydopamine lesions in the nigrostriatal neurones of rat brain.

Male rats showed a clear preference for one forepaw when they were trained to press a lever for food reward. The preference was then changed by training, by local anaesthetic injection into the preferred paw, by lesions in the striatal output pathways in the brain, or by neurotoxin injection into the striatum contralateral to the side of the preferred paw. The pressing rate was not changed in spite of the change in paw use in any of these operations. This result is in marked contrast to the effect of reducing the dopamine concentration on the side contralateral to the preferred paw; in this case a marked reduction in responding is seen as well as the change in paw use. Thus medial forebrain bundle 6-hydroxydopamine lesions are more debilitating than either striatal damage or peripheral paralysis at least in the short term.

Animals↗
PubMed1985

Different patterns of molecular forms of somatostatin are released by the rat median eminence and hypothalamus.

The molecular forms of somatostatin (SOM) released from hypothalamic slices and from the isolated median eminence (ME) in vitro were compared by high-performance liquid chromatography and radioimmunoassay. SOM-14 was the predominant form of the peptide released from hypothalamic slices, although small amounts of SOM-28 were detected. Perifusates of ME tissue contained a larger proportion of SOM-28 and higher molecular weight peptides were present; depolarization increased the rates of release of all molecular forms of SOM. These results suggest that the capacity to release SOM-28 and high-molecular-weight forms of SOM may be a specialized function of nerve terminals in the ME.

Animals↗
PubMed1984

Schneider's first-rank symptoms of schizophrenia. An association with increased growth hormone response to apomorphine.

Growth hormone and prolactin (PRL) responses to 0.75 mg of apomorphine hydrochloride were measured in 19 newly admitted psychotic patients who had been untreated by neuroleptic or antidepressant drugs for at least nine months. We compared hormonal responses between subgroups of patients who were distinguished using the diagnostic criteria of Feighner et al and Spitzer et al, and by the presence or absence of Schneider's first-rank symptoms of schizophrenia. We included nine healthy subjects who were matched by age and sex with the schizophrenic patients. Growth hormone responses to apomorphine were greater in patients with Schneider's first-rank symptoms than in those without first-rank symptoms, and were also greater than in control subjects. Suppression of plasma PRL was also greater in schizophrenic patients than in control subjects. These results support the dopamine hypothesis of schizophrenia.

Acute Disease↗
PubMed1983

The anatomical substrate of the turning behaviour seen after lesions in the nigrostriatal dopamine system.

Studies of the fibre connections of the substantia nigra suggest that the behavioural results of changes in the activity in the striatal dopamine-containing system are mediated by a pathway from the striatum to the substantia nigra and thence to the thalamus. Small discrete electrolytic lesions in the appropriate part of the crus cerebri interrupt the striatonigral axons without damage to the nigrostriatal system. Such lesions inhibit turning induced by activation of striatal dopamine receptors. Similarly, turning induced by apomorphine in rats lesioned with 6-hydroxydopamine is inhibited by damage to the ipsilateral ventromedial area of thalamus which receives fibres from the substantia nigra.

Afferent Pathways↗
PubMed1983

The electrophysiology of dopamine (D2) receptors: a study of the actions of dopamine on corticostriatal transmission.

Electrophysiological recordings from the cells of the neostriatum in rats anaesthetised with halothane revealed only inhibitory actions of dopamine applied iontophoretically close to the cells. Inhibition of cortical driving seemed to have a slightly higher threshold in most cells but dopamine inhibited spontaneous action potentials, glutamate-induced responses, and cortical driving in the cells studied. Fluphenazine applied iontophoretically blocked the actions of dopamine but was itself without effect on the neuronal responses. Sulpiride, in contrast, was without effect on the spontaneous activity of the cells and was ineffective in blocking the action of applied dopamine. Sulpiride, nevertheless, increased the response to cortical stimulation though it had no action on the response to applied glutamate. These results suggest that the sub-class of dopamine receptors on the terminals of the corticostriatal pathway may be inhibitory on glutamate release and preferentially sensitive to blockade by sulpiride.

Acetylcholine↗
PubMed1983

Oestradiol-17 beta increases the firing rate of antidromically identified neurones of the rat neostriatum.

Extracellular recordings were made from the neostriatum of rats anaesthetised with halothane. Normal male and female animals were used as well as castrated animals with implants containing oestradiol-17 beta (E2). In animals with high levels of circulating oestrogen, intact pro-oestrous rats and females and males bearing an E2 implant, individual units could be recorded that were spontaneously active and with axons that could be excited by stimulation in the crus cerebri. Such antidromically identified striato-nigral neurones were invariably silent in male animals and in ovariectomised females. In contrast to animals in pro-oestrus, intact female animals during metoestrus showed the 'male' pattern of striatal cell activity. These results show that E2 can stimulate spontaneous firing of striato-nigral neurons, and that this action of E2 is not sex-dependent.

Action Potentials↗
PubMed1982

Crossed connections of the substantia nigra in the rat.

The existence of crossed multisynaptic pathways that allow for the interdependent control of activity in one substantia nigra and its contralateral counterpart has been inferred from a number of recent biochemical and neurophysiological investigations. This prompted a reexamination of the connections of the substantia nigra with an emphasis on crossed inputs to and crossed projections from that nucleus. Male albino rats received 20-50-nl pressure injections of a 1% wheat germ agglutinin-conjugated horse-radish peroxidase (WGA-HRP) solution into the substantia nigra or into surrounding areas as controls. Following a 24-hour survival period the animals were processed according to the tetramethylbenzidine protocol for the visualization of HRP. The pattern of anterograde transport of WGA-HRP after substantia nigra injections, confirming for the most part previous reports, demonstrated ipsilateral nigral efferent projections to the striatum; globus pallidus; subthalamic nucleus; the lateral dorsal, paralamellar mediodorsal, ventromedial, and parafascicular thalamic nuclei; central gray, midbrain reticular formation; superior colliculus; and peribrachial area, including the pedunculopontine nucleus. Additionally, the nigral projections to the paralamellar mediodorsal and ventromedial thalamic nuclei and to the superior colliculus were demonstrated to be bilateral. Most of these connections were confirmed by the complementary retrograde experiment. In accordance with previous reports, intranigral WGA-HRP injections retrogradely labeled neurons located in the ipsilateral prefontal cortex, motor cortex, striatum, globus pallidus, central nucleus of the amygdala, anterior hypothalamic area, subthalamic nucleus, and dorsal raphe. Additionally, labeled perikarya were observed in the ipsilateral parafascicular thalamic nucleus, in the contralateral posterior lateral hypothalamic area, and in the ipsilateral and contralateral peribrachial-pedunculopontine area. These latter nigral afferents were confirmed with complementary WGA-HRP injections into each of the regions of origin. While bilateral peribrachial-pedunculopontine innervation of the substantia nigra has been reported in the cat there has been no previous demonstration of a crossed nigral afferent system from the contralateral posterior lateral hypothalamic area. The results are discussed with reference to the pathways that may mediate the interdependent control of the activity of neurons in the left and right substantia nigra. Additionally, the association of the substantia nigra with a variety of neuronal circuits, including the cerebellofugal, tectothalamic, thalamocortical, thalamostriatal, and basal ganglia pathways, are discussed.

Animals↗
PubMed1982

Increases in dopamine metabolism are not a general feature of intracranial self-stimulation.

Rats with electrodes implanted in the ventral tegmentum and posterior hypothalamus were trained to press a lever to obtain electrical stimulation through the electrodes. Stimulation in animals with ventral tegmental electrodes led to an increased concentration of homovanillic acid and dihydroxyphenylacetic acid in the forebrain of the animals. Stimulation in the posterior hypothalamus did not result in such raised concentrations in spite of the fact that the behaviour from the two sites was indistinguishable. Responding in the posterior hypothalamus was reduced by doses of neuroleptic drug similar to those reported to reduce responding in the ventral tegmental area.

Animals↗
PubMed1982

The effect of DSP-4 on some positively reinforced operant behaviors in the rat.

The effects of a new neurotoxin for noradrenergic (NA) neurons, DSP-4, on the acquisition, retention and extinction of positively reinforced operant responses were studied in rats. The acquisition of an L-shaped runway task for food reward, of a simultaneous light-dark discrimination in a Y-maze task and of a lever press response for food was not affected in DSP-4 treated animals. No deficit in retention behavior was found in the Y-maze task after DSP-4 treatment. The DSP-4 treated animals showed increased resistance to extinction in the L-shaped runway. However, the extinction of the lever press response for food (CRF) was unaffected in the same animals. In accordance with previous results, DSP-4 resulted in a widespread depletion of NA in cortex, hippocampus, cerebellum and spinal cord. One week after the DSP-4 administration, histochemical studies at the light microscopic level indicated that the cell bodies of the locus coeruleus remained intact in DSP-4 treated animals. Desipramine pretreatment provided only partial protection from the neurotoxic effects of DSP-4. The results are discussed in relation to the mechanism by which DSP-4 produced the long-term depletion of central NA ans with reference to the role of central NA neurons in behavior.

Amines↗
PubMed1982

Orthograde transport of Nuclear yellow: a problem and its solution.

Nuclear yellow injections into the striatum of rats led to staining of both neuronal and glial nuclei even after less than 24 h 'transport time'. The distribution of some of the glial nuclei suggested that the dye was being transported along the striato-nigral pathway. Staining in these areas was greatly reduced if kainic acid was co-injected with the Nuclear yellow.

Animals↗
PubMed1981

The role of dopamine in pontine intracranial self-stimulation: a re-examination of the problem.

Subsequent of their achieving stable rates of responding for electrical stimulation through electrodes implanted in the region of the brachium conjunctivum, rats were anaesthetized and 6-hydroxydopamine injected through an implanted guide tube into the area of lateral hypothalamus in which the ascending axons of dopamine-containing neurones are found. The resultant destruction of these axons had similar temporary effects on the behaviour of the animals whether it was ipsilateral or contralateral to the electrode. It is concluded that nigral or mesolimbic dopaminergic systems are not involved in pontine intracranial self-stimulation behaviour.

Animals↗