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S T Mason

Publications and source records attributed to S T Mason.

At least 19 recordsLinked to original sources
PubMed1985

Chronic administration of type A monoamine oxidase inhibitors increases duration of thiopentone anaesthesia in the rat.

Daily intraperitoneal administration for fifteen days of the mixed type A and type B monoamine oxidase inhibitors phenelzine, isocarboxazid, iproniazid and tranylcypromine caused a marked increase in the duration of thiopentone anaesthesia ('sleeping time') tested 48 hours after the last drug injection. This effect was not due to accumulation of drug or other carryover since it failed to occur after 5 days of daily administration. Similar prolongation of anaesthesia was seen after 15, but not 5 days of administration of the selective type A monoamine oxidase inhibitors clorgyline and LY 51641 but not with the type B inhibitors pargyline and deprenyl.

Anesthesia↗
PubMed1984

Chronic and acute administration of typical and atypical antidepressants on activity of brain noradrenaline systems in the rat thiopentone anaesthesia model.

A behavioural model sensitive to manipulation of brain noradrenaline systems and with characteristics of beta-receptor mediation has been developed using the duration of thiopentone anaesthesia in the rat. Acute and chronic administration of various antidepressant agents was examined. In the acute phase, (30 min prior to thiopentone) the noradrenaline uptake-inhibiting tricyclic drugs and viloxazine increased anaesthesia duration in a dose-dependent fashion. The atypical antidepressants trazodone, iprindole, and mianserin did this only weakly, while the dopaminergic and serotonergic uptake-inhibiting antidepressants (respectively bupropion, nomifensine, and zimelidine, fluoxetine) markedly shortened anaesthesia duration. Chronic administration (for 15 days) prolonged anaesthesia duration measured 2 or 5 days after the last drug injection for all tricyclic agents, for the atypical antidepressants mianserin, iprindole, fluoxetine, and zimelidine, and for viloxazine.

Anesthesia↗
PubMed1983

Anaesthesia: the role of adrenergic mechanisms.

The beta-blocker propranolol administered intraperitoneally to rats prior to the barbiturate anaesthetic thiopentone caused a dose-dependent increase in anaesthesia duration. Sotalol, which only poorly crosses the blood-brain barrier, had no such effect, implying a central site of action. The selective beta 1-blockers, metoprolol and atenolol, did not alter thiopentone anaesthesia duration; implying that the effect of propranolol was mediated by a beta 2-receptor. The selective alpha 1-blocker prazocin increased thiopentone anaesthesia duration, while the alpha 1-agonist ST 587 decreased it. Since the alpha 1-agonist methoxamine, which only poorly crosses the blood-brain barrier, was ineffective, a central site of action is indicated. The alpha 2-agonist clonidine markedly increased thiopentone-anaesthesia duration, while the alpha 2-blocker yohimbine, shortened the duration. These effects were shown to be noradrenergic since they were blocked by prior depletion of brain noradrenaline using 6-hydroxydopamine. A model is proposed in which drug-induced alterations in the firing of locus coeruleus cells, or drug-induced changes in the postsynaptic effect of released noradrenaline, may be responsible for modulation of cortical arousal, wakefulness and the processing of sensory stimuli; thus affecting the duration of barbiturate anaesthesia.

Adrenergic alpha-Antagonists↗
PubMed1983

Behavioural evidence that chronic treatment with the antidepressant desipramine causes reduced functioning of brain noradrenaline systems.

A behavioral system sensitive to the net functional activity of the locus coeruleus noradrenergic system, with characteristics of a beta-adrenoceptor mediated response, has been developed based on the duration of thiopentone anaesthesia in the rat. The effects of acute and chronic treatment with the tricyclic antidepressant desipramine (DMI) were determined. Acute DMI from 5 to 25 mg/kg increased thiopentone sleeping-time in a dose-dependent fashion. This was due to an action on noradrenergic systems, since it was mimicked by treatment with the selective neurotoxin 6-hydroxydopamine, which itself increased thiopentone sleeping-time and prevented any additional effect of DMI. Chronic treatment with DMI had no effect on thiopentone sleeping-time when carried out for 2 or 5 days but markedly prolonged it when carried out for 10 or 20 days, thus paralleling the time course of clinical action of the drug.

Animals↗
PubMed1983

Brain noradrenaline and anaesthesia: further characterization of the beta-receptor.

The sleeping time induced by thiopentone in rats was markedly prolonged by the (-)-isomer of propranolol while the (+)-isomer was virtually without effect. Since the two isomers are equipotent in their membrane-stabilizing effects but the (-)-isomer is about seven to ten times more potent than the (+)-isomer in beta-blockade this suggests that the potentiation of barbiturate sleeping time is due to blockade of beta-adrenergic receptors. The centrally active beta-agonist, clenbuterol, shortened thiopentone-induced sleeping time in a dose-dependent fashion while the beta-agonist, salbutamol, which fails to cross the blood-brain barrier, was without effect. This suggests a central locus of action. Destruction of the noradrenaline system in the locus coeruleus with 6-hydroxydopamine prevented the effect of a racemic mixture of propranolol in elevating thiopentone-induced sleeping time, thus confirming a noradrenergic mechanism and indicating that the coerulear, rather than the medullary, noradrenaline fibres were involved. Thiopentone-induced sleeping time was potentiated by the selective beta 2 blocker ICI 118551 but not by the selective beta 1 blocker, metoprolol, thus characterizing the relevant beta-receptor type as beta.

Anesthesia↗
PubMed1983

The neurochemistry and pharmacology of extinction behavior.

The role of various neurotransmitter systems in the brain in extinction behavior is examined. An attempt is made to suggest psychological mechanisms (such as attention, secondary reinforcement or internal inhibition) by which the neurotransmitter systems or drugs act to produce the observed alteration in extinction behavior. The putative neurotransmitters acetylcholine, noradrenaline, dopamine, serotonin, endorphins and the peptides are reviewed, as are pharmacological agents such as the benzodiazepines, the barbiturates, the psychodelics, the neuroleptics, the psychomotor stimulants and cannabinoids. Other treatments and factors are considered such as peripheral hormones and the adrenal-pituitary axis. It is suggested that the noradrenergic system may be involved in the expression of extinction behavior by a role in selective attention, the dopamine system via an involvement with secondary reinforcement, the cholinergic system by a mechanism of response inhibition and the barbiturates and benzodiazepines by a block of nonreward.

Acetylcholine↗
PubMed1983

Brain noradrenaline and varieties of alternation learning.

Depletion of noradrenaline from the locus coeruleus system was effected by intraperitoneal injection of 6-hydroxydopamine to neonatal rat pups. Spontaneous, and two paradigms of rewarded alternation behaviour were examined in a T-maze. No change was seen in spontaneous alternation but marked impairment in acquisition of one of the two rewarded alternation tasks was found. It is concluded that powerful support is offered to previous results using intracerebral adult 6-hydroxydopamine administration.

Animals↗
PubMed1983

Brain noradrenaline and anaesthesia: behavioural and electrophysiological evidence.

Neonatal administration of 6-hydroxydopamine to rat pups was used to deplete brain noradrenaline in the locus coeruleus projection system to less than 5% of normal and the response to barbiturate and non-barbiturate anaesthetics examined. The sleeping time in response to administration of thiopentone, pentobarbitone, methohexitone or hexobarbitone was markedly increased in 6-hydroxydopamine-treated rats, as it was for the non-barbiturates chloral hydrate and diisopropylphenol. The sleeping time for other non-barbiturates such as althesin, ketamine and ethyl carbamate (urethane) was not affected in noradrenaline-depleted rats. Similarly, an index of the evoked potential, recorded in the primary somatosensory cortex to supramaximal electrical stimulation of the forepaw, decreased more markedly with increasing doses of thiopentone in 6-hydroxydopamine-treated rats than in controls. Potentiation of the effect of diisopropylphenol on the evoked cortical response was also seen in noradrenaline-depleted rats while the effect of althesin did not differ. It is suggested that brain noradrenaline pathways originating from the locus coeruleus may play an important role in the duration and depth of anaesthesia resulting from barbiturate and some related agents.

Anesthesia, General↗
PubMed1980

Role of forebrain catecholamines in amygdaloid kindling.

The rate and pattern of seizure development provoked by repeated electrical stimulation of the amygdala (kindling) was assessed in rats that had been pretreated with intracerebral injections of the selective catecholaminergic neurotoxin 6-hydroxy-dopamine. Rats with selective depletion of forebrain noradrenaline displayed a highly significant facilitation of both primary-site and secondary-site kindling, whereas no such effect occurred in rats with selective depletion of forebrain dopamine. The facilitative effects of noradrenaline depletion were apparently related to disinhibition of the spread of seizure discharge from the stimulated site rather than to increased epileptogenicity in the stimulated site itself. These results are consistent with previous evidence that noradrenaline reduces the susceptibility of the central nervous system to epileptiform activity, and they suggest that a lessening of seizure-suppressant noradrenergic function in the forebrain might be part of the mechanism underlying kindling.

Amygdala↗
PubMed1980

Modulation of rat brain alpha- and beta-adrenergic receptor populations by lesion of the dorsal noradrenergic bundle.

Bilateral lesion of the ascending noradrenergic fibers in the dorsal bundle of adult Wistar rats with 4 micrograms 6-hydroxydopamine caused extensive depletion of norepinephrine in all forebrain areas, but led to a 54% increase in norepinephrine levels in the cerebellum. beta-Adrenergic receptor binding of [3H]dihydroalprenolol was significantly increased in all forebrain areas depleted of norepinephrine except hypothalamus. The increase in [3H]dihydroalprenolol binding was due to 62% and 34% increases in the number of beta-receptor sites in the frontal cerebral cortex and hippocampus respectively. Binding of [3H]WB-4101 to alpha 1-adrenergic receptors after dorsal bundle lesion was augmented generally to a lesser extent than beta-receptor binding, with significantly increased numbers of sites only in the frontal cortex (74%), thalamus (20%) and septum. Both alpha 1- and beta-receptor binding sites were reduced in number by 25-28% in the cerebellum of dorsal bundle-lesioned rats, whereas intraventricular administration of 6-hydroxydopamine to adult rats, which depletes norepinephrine in the cerebellum by 96%, increased cerebellar alpha 1- and beta-receptor binding by 33-40%. Binding of [3H]clonidine to forebrain alpha 2-adrenergic receptors was significantly elevated in the frontal cortex, but reduced in the amygdala and septum, after dorsal bundle lesion.

Amygdala↗
PubMed1980

Dorsal noradrenergic bundle and selective attention in the rat.

The role for the dorsal noradrenergic bundle (DNB) in selective attention and stimulus filtering was tested in several situations. The DNB was damaged by stereotaxically guided injections of 4 microgram of the neurotoxin 6-hydroxydopamine (6-OHDA). The latent inhibition effect was blocked by 6-OHDA-induced depletion of forebrain noradrenaline, whereas nonreversal shift performance was better in noradrenaline-depleted rats than controls. These data are interpreted to indicate that animals with DNB lesions are imparied in ignoring irrelevant stimuli. However, in situations in which control animals did not learn to ignore irrelevant stimuli, no lesion-induced difference was found. Thus, controls and animals with DNB lesions learned equally about each of two dimensions of a multiple-redundant discrimination task. This was assessed both by interpolated trials with only one dimension present and by shifts in which only one of the previous two dimensions remained relevant. It is concluded that the DNB lesion does not increase stimulus sampling globally but that it impairs performance only in those cases in which normal rats learn to ignore irrelevant stimuli.

Animals↗
PubMed1980

The use of conditioned suppression to evaluate the nature of neuroleptic-induced avoidance deficits.

Three groups (N = 8) of rats received five 10-trial sessions of one-way avoidance training in which each trial was initiated by a 10-sec tone stimulus and terminated either by a shuttle response during the tone (avoidance) or by a response during the electric shock (escape). Rats in groups treated with pimozide (0.5 or 1.0 mg/kg i.p.) failed to acquire to avoidance response although they escaped readily when shock was presented, whereas control rats consistently avoided the shock. The same rats then received several sessions of food-reinforced lever-pressing in a different apparatus; no drugs were given during these sessions. When responding had stabilized, the tone that had signalled shock in the avoidance sessions was presented for a 1-min period. A significant decrease in responding during the tone was observed in all groups when compared to unshocked controls, demonstrating that the pimozide-treated rats, although failing to acquire the avoidance response in the shuttle box, had learned the association between the tone and shock. The results suggested that the neuroleptic-treated animals failed to avoid because of a deficit in the ability to initiate responses rather than a deficit in associative learning.

Animals↗