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I C Kilpatrick

Publications and source records attributed to I C Kilpatrick.

46 records · Page 3Linked to original sources
PubMed1982

Presynaptic muscarinic receptors on dopaminergic terminals in the nucleus accumbens.

Levels of muscarinic receptors were measured in the nucleus accumbens of rat following 0.8 microgram 6-hydroxydopamine or vehicle injections (0.2 microliter into the ventral tegmental area to investigate whether the dopaminergic terminals destroyed by this procedure bear muscarinic receptors. Dopamine levels in the nucleus accumbens ipsilateral to the injection of 6-hydroxydopamine were substantially reduced by 83% as compared to the unlesioned side after 7 days. Significant decreases in the specific binding of [3H]N-methylscopolamine of 9 and 15% were also seen in the nucleus accumbens ipsilateral to the lesion after 7 and 14 days respectively. The class of muscarinic receptor depleted by the lesion was further investigated using [3H]oxotremorine-M to label the 'super high' affinity binding sites. The percentage occupancy of total muscarinic receptors by [3H]oxotremorine-M was significantly decreased by lesion e.g. 23% after 7 days indicting a selective loss of 'super high' affinity binding sites. The lesion caused no change in the affinity constant for the muscarinic antagonist, propylbenzilylcholine. Studies of the binding of the agonist carbachol and oxotremorine-M by competition with [3H] propylbenzilylcholine showed little change in the concentrations or affinity constants of the 'high' and 'low' affinity binding sites with the 6-hydroxydopamine lesion.

Animals↗
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

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↗