PubMed Health⌕ Search

Biomedical subjects

S T Mason

Publications and source records attributed to S T Mason.

At least 19 recordsLinked to original sources
PubMed1979

Regional topography within noradrenergic locus coeruleus as revealed by retrograde transport of horseradish peroxidase.

A hitherto unsuspected degree of regional topographic organization in the noradrenergic nucleus, locus coeruleus, was revealed by the use of retrograde transport of horseradish peroxidase (HRP) from terminal areas receiving noradrenergic innervation. HRP was injected into hippocampus, hypothalamus, thalamus, caudate-putamen, septum, amygdala-piriform cortex, cerebellum and cortex. Successful transport was obtained from all areas, including the caudate-putamen and cerebral cortex. The pattern of HRP positive cells in the ipsilateral locus coeruleus was markedly different depending on the location of the HRP injection. Thus, hippocampal injections labeled cells in the dorsal locus coeruleus but not at all in the ventral tip. Injections of HRP into caudate-putamen or cerebellum labeled the ventral tip along with the rest of the dorsal portion. HRP injections into the septum labeled cells only in the dorsal half of the dorsal locus coeruleus. There thus exists a three tier division of locus coeruleus into the ventral one third, dorsal one third and intermediate one third. A further division was seen in the anterior-posterior plane with HRP injections into the thalamus labeling the posterior pole of locus very intensely but with little transport to more anterior levels; conversely HRP injection into the hypothalamus resulted in intense labeling only in the anterior pole of locus coeruleus. Amygdala-piriform cortex HRP injections revealed a further pattern with very intensely reactive cells scattered sparsely throughout the nucleus. Cortical HRP injections yielded weaker labeling also in occasional, scattered cells. All HRP transport to locus coeruleus was shown to be noradrenergic by degeneration with 6-hydroxydopamine and due to terminal, rather than fiber of passage, uptake by control injection into the dorsal NA bundle. It is concluded that the locus coeruleus is not an homogenous nucleus with respect to the origin of the noradrenergic projections to sundry forebrain, spinal and cerebellar areas but is comprised of distinct subdivisions of noradrenergic neurons.

Amygdala↗
PubMed1979

Catecholamines and convulsions.

Severe depletion of brain noradrenaline and separately of brain dopamine was induced in rats by intracerebral injection of the selective neurotoxin 6-hydroxydopamine, and the susceptibility of the treated animals to various seizure-inducing manipulations was examined. A significant potentiation of the seizures induced both by Metrazol and by electroconvulsive shock was found in animals depleted of brain noradrenaline, but no alteration was seen after depletion of brain dopamine on either measure. The catecholaminergic drug cocaine also induced seizures, but these were found not to depend on either brain noradrenaline or dopamine as they continued to occur in the virtual absence of either catecholamine. It is concluded that cocaine induces seizures by a non-specific toxic mechanism and that noradrenaline, but not dopamine, is involved in reducing the suceptibility of the central nervous system to the several distinct forms of seizure induction examined.

Animals↗
PubMed1979

Physiological function of descending noradrenaline projections to the spinal cord: role in post-decapitation convulsions.

Destruction of the descending noradrenergic innervation to the spinal cord, but not that to the cerebellum or the forebrain, by the use of intracerebral injection of 6-hydroxydopamine completely prevented the occurrence of the usual itation convulsion. Depletion of brain noradrenaline by synthesis inhibition with DDC, FLA 57 or FLA 63 g reduced the duration of the post-decapitation convulsion. Blockade of alpha-noradrenergic receptors by phentolamine or phenoxybenzamine, but not of beta-receptors by propranolol, also reduced the duration of the convulsion. The presynaptic alpha-agonist, clonidine, at either 1 mg/kg or 0.05 mg/kg also reduced the magnitude of the convulsion but either blockade of dopamine receptors with pimozide or destruction of the ascending dopamine systems by 6-hydroxydopamine was without effect. It is concluded that dopamine systems are not involved in post-decapitation convulsions and that the noradrenergic involvement is by the descending spinal projections acting on a post-synaptic alpha-receptor in the spinal cord, but also modulated by presynaptic alpha-receptors possibly on the locus coeruleus perikarya.

Animals↗
PubMed1979

On the specificity of kainic acid.

The specificity of the neurotoxic agent, kainic acid, for destroying cell bodies while sparing terminals and fibers of passage was examined by infusing this agent into the axons of the dorsal noradrenergic bundle and measuring the degree of depletion of noradrenaline concentrations and the reduction in noradrenaline uptake in cortex and hippocampus. Extensive neuronal loss and gliosis were observed around the injection site. In addition, a significant and consistent 25 percent depletion of hippocampal-cortical noradrenaline was also obtained. The results suggest that although kainic acid has its greatest destructive action on neuronal perikarya, a significant amount of damage to axons of passage may also occur.

Adrenergic Fibers↗
PubMed1979

The dorsal bundle extinction effect:dependence on subtle changes in acquisition.

Destruction of the ascending noradrenergic innervation to the forebrain in rats by intracerebral injection of the selective neurotoxin 6-hydroxydopamine (4 microgram in 2 microliter injected bilaterally into the dorsal bundle in the mesencephalon) was found to cause resistance to extinction of a continuously reinforced lever press response. However, this effect occurred only if the lesion were present during acquisition training on the reinforced schedule and not if intact animals were trained and the lesion inflicted after completion of acquisition training and just prior to the extinction phase. Thus, the behavioural effect that manifests itself during extinction appears to be due to subtle changes in the acquisition learning process. This is consistent with the predictions of an attentional theory of noradrenergic function and appears to exclude most other suggested explanations of the dorsal bundle extinction effect.

Animals↗
PubMed1979

Noradrenaline, fear and extinction.

It has been suggested that noradrenaline in the central nervous system is involved in fear and anxiety. To test this postulate extensive depletion of ascending noradrenaline systems was accomplished by intracerebral injection of the selective neurotoxin 6-hydroxydopamine. Fear and anxiety were assessed using a Sidman avoidance task and a conditioned emotional response paradigm. No alteration in fear motivated acquisition learning of either of these tasks were detected. Resistance to extinction was seen on the conditioned emotional task, perhaps because of its continuously reinforced nature, but not on the Sidman avoidance, perhaps as a consequence of the reinforcement contingencies which render this task more similar to a partially reinforced schedule. No evidence for a role of ascending noradrenaline systems in fear or anxiety was hence obtained, but a further demonstration of a role in extinction processes was found.

Animals↗
PubMed1979

Noradrenergic processes involved in the locomotor effects of ethanol.

Male albino Wistar rats were depleted of forebrain noradrenaline by intracerebral injection of 4 microgram of 6-hydroxydopamine into the noradrenaline bundles in the mesencephalon. The locomotor response was examined in response to intraperitoneal injection of ethanol. The locomotor stimulation by 0.1 g/kg ethanol was not altered by the lesion, whereas the sedation found in response to 1 g/kg in controls failed to occur in the lesioned rats and instead a stimulation was seen.

Animals↗
PubMed1979

Noradrenaline and avoidance learning in the rat.

The selective neurotoxin 6-hydroxydopamine was used to deplete forebrain noradrenaline to less than 5% of control values and the learning capabilities of the depleted animals examined on a two-way active avoidance task. Noradrenaline depleted animals learned the two-way active avoidance task more quickly than controls and required fewer training trials to reach acquisition criterion. Twenty-four hour retention was not altered by the lesion, but significant resistance to extinction was seen when electric footshock was no longer presented. More detailed analysis of the improved acquisition shown by the lesioned animals revealed that the major effect lay in a reduced freezing response to footshock. This freezing tended to slow down learning in the control animals, since it was incompatible with the required two-way active avoidance response. No alteration was seen in sensory detection thresholds for electric footshock or in spontaneous locomotor activity in the absence of shock. These results are discussed in relation to theories of noradrenaline function in learning and memory and, more recently, in fear and anxiety.

Animals↗
PubMed1979

The dorsal noradrenergic bundle and varieties of passive avoidance.

Neither acquisition learning nor 24-h retention was significantly altered by 6-hydroxydopamine intracerebral injections which depleted forebrain noradrenaline (NA) to less than 5% of control values. The absence of passive avoidance impairment cannot be ascribed to functional recovery following the lesion (indicated by testing 24 h post-operation) and by using the F-344 strain of rat which does not show denervation supersensitivity as measured by NA-sensitive adenylate cyclase. Nonassociative freezing to electric footshock, changed by the injections, resulted in slower acquisition at a footshock level 4 mA, but not at 1 mA.

Adenylyl Cyclases↗
PubMed1979

Central noradrenergic--cholinergic interaction and locomotor behavior.

Depletion of forebrain noradrenaline by intracerebral injection of 4 micrograms of 6-hydroxydopamine into the fibres of the dorsal noradrenergic bundle was found to block the cataleptic effects of the muscarinic cholinergic agonist arecoline and to potentiate the locomotor stimulant effects of the muscarinic cholinergic blocker scopolamine. The nicotinic drugs, mecamylamine, a nicotinic blocker, and nicotine itself were unaffected in their actions by the depletion of forebrain noradrenaline. It is concluded that a noradrenergic--cholinergic interaction of the muscarinic type exists in brain and may have a function in the control of arousal, with catalepsy at one extreme and locomotor stimulation at the other.

Acetylcholine↗
PubMed1979

Dorsal bundle extinction effect: motivation or attention?

Male albino Wistar rats were injected bilaterally with 4 micrograms of 6-hydroxydopamine into the dorsal noradrenergic bundle to deplete forebrain noradrenaline to less than 5% of control values. Acquisition learning of a fixed interval schedule or a continuously reinforced schedule was not altered but resistance to extinction was seen after food reinforced training on either schedule but not after water reinforced training. A possible increase in food motivation was tested by the use of preloading with free food prior to a fixed interval session but both control and lesioned rats reacted similarly to this manipulation thus appearing to exclude an increase in food motivation. An attentional explanation is proposed and tested by the demonstration that resistance to extinction does not occur after a partially (variable ratio 4), as opposed to a continuously, reinforced schedule. Further evidence in favour of an attentional mechanism comes from the finding that on both a fixed interval and a continuously reinforced schedule the lesion has to be present during the acquisition phase to result in subsequent resistance to extinction. Intact animals trained on either schedule and subsequently subjected to the lesion failed to show an increased resistance to extinction.

Animals↗
PubMed1979

Interaction of brain noradrenaline and the pituitary-adrenal axis in learning and extinction.

The effect of 6-hydroxydopamine-induced degeneration of the dorsal tegmental noradrenergic (NA) projection alone or in combination with the removal of the adrenal glands was examined on several behavioral tasks. No impairment of acquisition on a continuously reinforced lever pressing response for food reward was seen as a result of the combined treatment. However, resistance to extinction was observed after depletion of forebrain noradrenaline on its own and this effect was prevented by the adrenalectomy. Adrenalectomy on its own failed to affect extinction. Acquisition of a passive avoidance task was slightly impaired after forebrain noradrenaline depletion but only the group with combined noradrenaline loss and adrenalectomy showed a 24 hour retention deficit. No alteration in shock thresholds was found in any group although both adrenalectomized groups consumed less food and were slightly less active in locomotor cages. It is suggested that previous reports of acquisition and retention deficits in avoidance tasks after combined dorsal NA bundle lesions and adrenalectomy are due to alterations in fear motivation rather than to a general learning impairment.

Animals↗