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M S Starr

Publications and source records attributed to M S Starr.

At least 91 records · Page 5Linked to original sources
PubMed1982

Multifocal brain sites for apomorphine-induced circling and other stereotyped motor behaviour in the 6-hydroxydopamine-lesioned rat.

Rats pretreated with 6-hydroxydopamine (6-OHDA, 8 micrograms in 4 microliters) in one medial forebrain bundle exhibited an assortment of stereotyped activities and pronounced circling towards the unlesioned side when apomorphine was administered either subcutaneously (0.5 mg/kg), or by discrete stereotaxic injection (5 micrograms in 0.2 microliter) into the caudate nucleus, nucleus accumbens, amygdala, lateral habenula, ventromedial thalamus, substantia nigra zona reticulata, periaqueductal grey or superior colliculus (but not a variety of other areas) ipsilateral to the lesion. These rotational responses were absent in unlesioned animals and, where tested, were attenuated by intraperitoneal haloperidol (0.5 mg/kg). It is suggested that multiple brain sites become sensitive to apomorphine following dopamine depletion by 6-OHDA.

Amygdala↗
PubMed1982

Evidence for the participation of nigrotectal gamma-aminobutyrate-containing neurones in striatal and nigral-derived circling in the rat.

The gamma-aminobutyrate-containing nature of nigrotectal neurones and the possible involvement of the tectum in circling behaviour were investigated in the rat. Electrolytic or kainic acid lesions of the substantia nigra reduced gamma-aminobutyrate levels on average by 19-29% in intermediate and deep, but not superficial superior colliculus. Placement of lesions or injection of muscimol (40 ng) into these gamma-aminobutyrate-innervated layers of superior colliculus gave only weak ipsilateral posturing or circling that was intensified by apomorphine, but which strongly antagonized contraversive apomorphine-induced circling in 6-hydroxydopamine pretreated rats(lateral greater than medial sites). Contraversive circling to unilateral muscimol (40 ng) was significantly attenuated by lesions or muscimol injections placed in the ipsi- or contralateral superior colliculus. Picrotoxin (40 ng) and tetanus toxin (30 mouse LD50 doses) evoked explosive motor behaviour from medial colliculus and vigorous contraversive circling when injected into the lateral colliculus. The latter offset ipsiversive asymmetries to kainate (0,8 micrograms) in the corresponding substantia nigra. Bilateral intratectal picrotoxin produced hyperactivity that reversed haloperidol catalepsy. Similar bilateral administration of muscimol did not produce catalepsy but a state of frozen immobility. Kainic acid introduced into the superior colliculus gave mixed excitatory-inhibitory responses initially followed by ipsiversive circling only and loss of tectal perikarya. None of these drug effects occurred from the overlying cerebral cortex or subjacent tegmentum. We propose that separate medial "non-postural" and lateral "postural" tectal locomotor regions may exist in the superior colliculus that are situated within a striato-nigrotectal outflow system capable of influencing the animal's motor activity and posture.

Animals↗
PubMed1981

Bilateral asymmetry in brain GABA function?

The GABA system was studied in different regions of the rat's brain following inhibition of brain GABA catabolism with intracisternal ethanolamine-O-sulphate or intraperitoneal aminooxyacetic acid. Both treatments lowered GABA aminotransferase and glutamate decarboxylase activities to similar extents in equivalent nuclei on either side of the brain. However, GABA contents were elevates to a consistently higher level in the right-hand substantia nigra, superior colliculus and nucleus accumbens, and in the left-hand ventral tegmentum, ventromedial thalamus and caudate nucleus, with no bilateral asymmetry evident in globus pallidus. These findings are discussed with reference to possible inherent inequalities in the functional states similar GABA systems on opposite sides of the brain.

4-Aminobutyrate Transaminase↗
PubMed1981

Involvement of dopamine in circling responses to muscimol depends on intranigral site of injection.

The intensity, direction and dopamine dependence of circling behaviour were determined following stereotaxic injections of 40 ng muscimol (in 0.2 microliter over 3 min) into different regions of the rat's substantia nigra (SN). Weak, haloperidol-sensitive ipsilateral postural or locomotor asymmetries were invariably obtained from the rostral SN zona compacta (SNC), whilst robust contraversive rotational behaviour was always initiated from the SN zona reticulata (SNR) and caudal SNC. This was most rapid from the central SNR and was markedly attenuated by i.p. pretreatment with haloperidol (0.1 mg/kg) or pimozide (0.25 mg/kg), or by week-old 6-OHDA lesions of the nigrostriatal dopamine (DA) tract. Turning was significantly weaker from the lateral and ventral areas of the SNR, where it was not susceptible to DAergic blockade. Lower circling rates were also obtained if the SNR injections were made rapidly (in 30 sec), in a large volume (0.5 microliter) or at a supramaximal dose level (400 ng), possibly due to increased spread of the drug to remote neurones having an opposite effect on directional behaviour, or to exaggerated stereotypy. The variable action of muscimol at multiple sites in the SN is suggested to account for the earlier conflicting data in the literature.

Animals↗
PubMed1981

The nucleus tegmenti pedunculopontinus and circling behaviour in the rat.

Lesioning the rat's substantia nigra (SN) with kainic acid (0.8 microgram) or by electrocoagulation (1 mA for 6 sec) significantly lowered GABA and glutamate decarboxylase levels at the treatment site, but not in the nucleus tegmenti pedunculopontinus (PPN), suggesting nigro-PPN fibres do not synthesize or store GABA. Stereotaxic injection of one PPN with muscimol (40 ng), picrotoxin (40 ng) or tetanus toxin (30 mouse LD50 doses) had little or no effect on the animals' behaviour; kainate caused ipsilateral body flexion, sporadic ipsiversive circling and contraversive barrel-rolling. These behavioural abnormalities disappeared after 7 days when histology confirmed virtually complete loss of PPN perikarya, intense gliosis and some demyelination of passing axons. Impairing PPN transmission with kainate (chronically) or muscimol (acutely) caused weak apomorphine-induced contraversive rotation, but did not modify the robust nigral muscimol-evoked contraversive asymmetry. While we do not exclude a role of PPN in motor control, these data suggest that nigro-PPN neurones are neither GABAergic nor mediators of central dopaminergic function.

Animals↗
PubMed1980

Specificity of GABA as a stimulator of dopamine release in rat substantia nigra.

The effects of amino acids and the benzodiazepine, flurazepam, on spontaneous and potassium-stimulated [3H]dopamine (DA) release were studied in slices of rat substantia nigra. None of the amino acids tested liberated [3H]DA directly. Flurazepam increased [3H]DA output by 51% and this effect was partially blocked by bicuculline but not by picrotoxin. GABA, L-glutamate and flurazepam, but none of the other compounds, potentiated the release of [3H]DA evoked by 20 mM KCl. The facilitation produced by flurazepam, but not by GABA or L-glutamate, was weakly antagonized by bicuculline and not picrotoxin. GABA did not modify the efflux of [3H]DA induced by low Na+, veratridine, ouabain, calcium ionophore A 23187, amphetamine or exogenous DA.

Amino Acids↗
PubMed1980

Evidence for a GABAergic nigrothalamic pathway in the rat. I. Behavioural and biochemical studies.

Unilateral stereotaxic microinjection of muscimol into the caudal region of the substantia nigra (SN) evoked tight, dose-related contralateral locomotor asymmetry and stereotypy. These behaviours were partially attenuated by various pretreatments, including 6-hydroxydopamine lesions of the nigrostriatal dopamine pathway, intraperitoneal (i.p.) haloperidol, and inhibition of thalamic GABA-transaminase activity by local intrathalamic injection of ethanolamine-O-sulphate. Electrolytic or kainic acid lesions of the medial thalamic nuclei (MTN) partially reduced the contraversive rotation to intranigral muscimol, and completely abolished the similar behaviour elicited by apomorphine (25 microgram) injected into the ipsilateral caudate nucleus. Contraversive turning to intranigral muscimol was completely inhibited by kainic acid lesions of the ipsilateral SN, but potentiated by intrahalamic injection of picrotoxin. Muscimol (40 ng--4 microgram) administered to the MTN complex in one hemisphere stimulated rats to move in ipsilateral circles that were unaffected by haloperidol. The results of these behavioural experiments suggest that the nigrostriatal dopamine pathway, the nigrothalamic projection and possibly other non-dopaminergic SN efferents all play important roles in mediating the influences of the SN on motor and stereotyped behaviours. Disruption of the nigrothalamic pathway following electrical or chemical injury to the SN was accompanied by falls in GABA and its synthesising enzyme in the corresponding MTN. These data, together with the findings of our electrophysiological study presented in the following paper, are consistent with the nigrothalamic system having a GABAergic inhibitory function.

Animals↗
PubMed1980

Evidence for a GABAergic nigrothalamic pathway in the rat. II. Electrophysiological studies.

Extracellular recordings were made from neurones in the ventromedial and parafasicular nuclei of the rat thalamus, many of which had demonstrable capsular or caudate projections. These cells responded to electrical stimulation of the ipsilateral substantia nigra with a short latency (4 ms) inhibition presumed to be monosynaptic. This inhibitory response was often preceded by a brief period of increased excitability (latency approximately 3 ms) attributed to activation of corticofugal collaterals. Longer latency, presumably oligosynaptic excitations (latency approximately 8 ms) and inhibitions (approximately 18 ms) were also obtained, but were more commonly evoked in non-projection neurones. All units were inhibited by iontophoretically applied GABA, glycine or 5-HT. Short and long latency synaptic and GABA-induced inhibitions were selectively blocked by bicuculline. Strychnine only antagonised glycine, while 5-HT was not affected by either convulsant. Intranigral injection of muscimol greatly elevated the spontaneous discharge rate of thalamic neurones, particularly those with a striatal projection. These data are compatible with nigrothalamic neurones maintaining a tonically active, GABA-mediated inhibition of cells in the ventromedial and parafascicular nuclei of the thalamus. It is speculated that intranigral muscimol indirectly activates these thalamic cells and thereby initiates contraversive circling behaviour by suppressing this inhibitory system.

Animals↗
PubMed1980

Rotational behaviour elicited by 5-HT in the rat: evidence for an inhibitory role of 5-HT in the substantia nigra and corpus striatum.

Unilateral intranigral microinjection of 5-HT or Wy 25093, a selective inhibitor of 5-HT uptake, elicited ipsiversive circling and a fall in striatal dopamine (DA) turnover. Conversely intranigral methysergide or unilateral lesions of the raphé-nigral 5-HT pathway produced contraversive turning and/or increased DA turnover. Both types of behaviour were accentuated by nialamide and attenuated by haloperidol. Caudate injections of 5-HT or Wy 25093 provoked contraversive turning which was increased by nialamide and hyoscine, partially diminished by haloperidol and antagonized by eserine. Ipsiversive circling was induced by intracaudate methysergide, which was potentiated by nialamide and eserine, unaffected by haloperidol and depressed by hyoscine. It is proposed that 5-HT normally subserves an inhibitory function both in the substantia nigra and corpus striatum.

Animals↗
PubMed1979

Is glycine an inhibitory synaptic transmitter in the substantia nigra?

Nigral tissue accumulated 14C-glycine by an energy-, temperature- and sodium-dependent mechanism; the transport process was inhibited by small neutral amino acids and had an apparent Km of 143 microM and Vmax of 787 nmol/g/min. Re-release of accumulated 14C-glycine was initially extremely rapid (40% in first 5 min) and subsequently accelerated by +40 mM K+ in a Ca2+-dependent manner. Intranigral kainate (0.25 microgram) lowered the levels of striatal DA (63%) and nigral GABA (25%) ipsilaterally, but not nigral glycine. Injections of glycine or strychnine (10--100 micrograms) into one SN induced slow ipsiversive or contraversive turning respectively. The evidence for glycine as a neurotransmitter in SN is discussed.

Amino Acids↗
PubMed1979

GABA-mediated potentiation of amine release from nigrostriatal dopamine neurones in vitro.

The uptake and release of 3H-dopamine was studied in slices of corpus striatum and substantia nigra in the presence of nialamide. High potassium triggered the outflow of tritium in both brain structures and this release was potentiated by GABA in a dose related fashion, whereas the spontaneous overflow of radioactivity was unchanged. This action of GABA was mimicked by the GABA-T antagonists aminooxyacetic acid and ethanolamine-O-sulphate, but not by the GABA analogues muscimol, 3-aminopropanesulphonic acid, gamma-hydroxybutyrate or beta-(p-chlorophenyl)-GABA. The response to GABA was not blocked by picotoxin, which itself facilitated the evoked release of 3H-dopamine, nor by bicuculline or the omission of calcium ions from the bathing medium. GABA facilitation of K+-evoked 3H-dopamine release was increased significantly on reducing tissue thickness and following prolonged incubation with GABA. GABA also potentiated the depolarization induced outflow of 3H-noradrenaline, 3H-5-hydroxytryptamine and 3H-histamine without affecting their initial accumulation. Veratridine, amphetamine and cold dopamine also raised the output of 3H-dopamine, but none of these releases was altered by GABA. The uptake of 3H-dopamine, but not that of 14C-GABA, was considerably attenuated in 6-hydroxydopamine lesioned corpora striata. The possible mechanism(s) of this stimulatory action of GABA is discussed.

4-Aminobutyrate Transaminase↗
PubMed1979

Effects of substance P injected into the substantia nigra.

1 Behavioural and biochemical effects of substance P (SP, 1 to 10 mug) administered in a small volume to discrete areas of the rat's brain were studied by means of a refined microinjection technique.2 SP injected unilaterally into the zona reticulata of the substantia nigra elicited dose-dependent contraversive circling and an increase in dopamine turnover in the ipsilateral striatum. SP applied to the zona compacta or zona lateralis, or to the medial lemniscus, evoked ipsiversive turning with a fall in dopamine turnover and a rise in 5-hydroxytryptamine (5-HT) turnover in the corresponding striatum.3 In both cases the onset of turning was immediate, reached a peak at about 5 min and lasted for 10 min. Both types of behaviour were blocked by haloperidol and exaggerated by nialamide.4 Unilateral injections of SP given into the crus cerebri, zona incerta, caudate nucleus, putamen or globus pallidus did not modify the animal's behaviour.5 In rats pretreated with apomorphine or amphetamine, SP induced contraversive circling which was followed by locomotion in the opposite direction.6 Turning responses to a second dose of SP were diminished at 3 h and reproducible at 24 h after the first injection.7 Bacitracin (50 ng) injected into the zona reticulata caused ipsiversive turning. Larger intranigral doses of bacitracin (10 mug), as with intracisternal SP (10 mug), evoked ;barrel rotation'.8 No changes in the free concentrations of aspartate, glutamate, gamma-aminobutyric acid, glycine or alanine were detected in any brain region following an intracisternal injection of 10 mug SP, although glutamine levels were elevated throughout the brain 30 to 60 min later.

Animals↗