Effect of chloral hydrate anaesthesia on the cerebral metabolic response to apomorphine administration.
Explore the source record for details and available documents.
Anesthetics↗
Biomedical subjects
J McCulloch
Publications and source records attributed to J McCulloch.
Cerebral circulatory and metabolic effects of piribedil.
Two aspects of the cerebrovascular action of the putative dopaminergic agonist, piribedil, have been examined. The vasomotor responses of isolated feline middle cerebral artery to piribedil and its metabolite, S584, were first examined and the effects of piribedil upon cerebral blood flow, cerebral oxygen consumption and the electroencephalogram (EEG) were then investigated in anaesthetised baboons. Neither piribedil nor S584 displayed any marked vasomotor efficacy in vitro, with small changes in tension being observed only with large concentrations (greater than 10(-4) M). In the anaesthetised baboons, the administration of piribedil (0.1 and 1 mg/kg, i.v.) resulted in significant increases in cerebral blood flow (40 +/- 10% and 49 +/- 14%, respectively) (mean +/- S.E.M.) and cerebral oxygen consumption (13 +/- 10% and 17 +/- 6%) which were accompanied by an increase in low voltage fast activity of the EEG. Prior administration of the putative dopaminergic antagonist, pimozide (0.5 mg/kg), which itself was without significant effect upon cerebral blood flow and oxygen consumption, prevented the cerebral circulatory, metabolic and EEG alterations induced by piribedil (1 mg/kg). It would appear likely that the action of piribedil upon cerebral metabolic activity was principally responsible for the increases in cerebral tissue perfusion which followed its administration.
Animals↗
Influence of dopaminergic systems on the lateral habenular nucleus of the rat.
The alterations in glucose utilization in the lateral habenular nucleus following the systemic administration of a putative dopaminergic agonist and antagonist have been examined in 48 rats by means of the autoradiographic 2-deoxyglucose technique. The administration of apomorphine (0.15--5 mg/kg) resulted in significant dose-dependent reductions (by 25 +/- 5% following 0.5 mg/kg) in glucose utilization in the lateral habenula. Haloperidol administration (0.01--10 mg/kg) was associated with increased (by 46 +/- 17% with 0.1 mg/kg) glucose utilization in the lateral habenula. The effects of apomorphine upon metabolic activity in the lateral habenula can be prevented by the prior administration of haloperidol (0.1 mg/kg). These observations provide evidence that metabolic activity in the lateral habenula, a nucleus occupying a strategic position between the forebrain and the mesencephalon, may be regulated by the activity in dopaminergic systems.
Animals↗
Retina-dependent activation by apomorphine of metabolic activity in the superficial layer of the superior colliculus.
Studies of the effect of the dopamine agonist apomorphine on local cerebral glucose utilization by means of the carbon-14-labeled deoxyglucose method demonstrate a dose-dependent metabolic activation in the superficial layer of the superior colliculus in the rat. Apomorphine stimulated glucose utilization in a number of other cerebral structures, but only the effect in the superficial layer of the superior colliculus depended on an intact retinal input. This effect was present with the animal in the light or in the dark, but was abolished by enucleation, which left the effects in other cerebral structures unimpaired. Activation of the superificial layer of the superior colliculus appears, therefore, to be secondary to an action of apomorphine on dopaminergic systems within the retina.
Animals↗
Cerebral circulatory and metabolic effects of vasoactive intestinal polypeptide.
Two aspects of the action of vasoactive intestinal polypeptide (VIP) within the cerebral vascular bed have been examined. First, in anesthetized rats, the vasomotor responses of individual pial arterioles on the convexity of cerebral cortex to the perivascular microinjection of vasoactive intestinal polypeptide were examined and, second, in anesthetized baboons, the effects of VIP on cerebral blood flow, cerebral oxygen consumption, and the electroencephalogram (EEG) were investigated both prior to and following the osmotic opening of the blood-brain barrier. The perivascular microinjection of VIP resulted in statistically significant increase in arteriolar caliber in the concentration range 10(-9) to 10(-6) M. For example, arteriolar caliber was increased by 22 +/- 3% (mean +/- SE) following the injection of VIP (10(-8) M). In the second series, in baboons, the intracarotid infusion of vasoactive intestinal polypeptide (10(-11) mol/min) did not affect cerebral blood flow, cerebral oxygen consumption, or the EEG under normal circumstances. If the same concentration of vasoactive intestinal polypeptide was administered following hypertonic opening of the blood-brain barrier, cerebral blood flow and oxygen consumption were both elevated (by 37 +/- 7% and 28 +/- 10%, respectively), accompanied by increased EEG activity.
Animals↗
Biochemistry: a protective device.
Explore the source record for details and available documents.
Blood Proteins↗
Specific distribution of metabolic alterations in cerebral cortex following apomorphine administration.
The topographic distribution of dopaminergic receptors in the cerebral cortex closely parallels that of the dopaminergic innervation. In the rat, dopaminergic axons which originate in the mesencephalon are confined to a few discrete regions of the neocortex--anterior cingulate cortex, entorhinal cortex, frontal cortex (particularly anteromedial and supragenual areas) and the transitional zone between the neocortex and the pyriform cortex. Moreover, biochemical examinations of processes generally considered to be indicative of dopaminergic neuro-transmission--neuronal uptake of labelled dopamine or dopamine-activation of adenylate cyclase activity--have confirmed a highly restricted locus of action of dopaminergic systems in the cerebral cortex. We describe here data obtained using the 2-deoxyglucose technique in conjunction with conventional neuropharmacological techniques, suggesting that the influence of dopaminergic systems on cortical function extends beyond the known confines of the mesocortical dopaminergic system.
Animals↗
Effects of apomorphine upon local cerebral blood flow.
The effects of apomorphine (0.1 mg/kg) upon local cerebral blood flow were examined in anaesthetized baboons. Proportionately similar increases in local cerebral blood flow were observed following apomorphine in the caudate nucleus (40%), cerebral cortex (38%) and cerebellar cortex (26%), despite the marked differences in the density of the dopaminergic innervation to these structures.
Animals↗
Factors influencing the response of the cerebral circulation to phenylethylamine.
The cerebrovascular actions of phenylethylamine, an amine that has been implicated in the pathogenesis of migraine, were investigated in 16 anesthetized baboons. The influence of monoaminergic blocking agents and of a specific inhibitor of monoamine oxidase upon the cerebral circulatory and metabolic actions of phenylethylamine were examined. The reductions in cerebral blood flow (28 percent) and cerebral oxygen consumption (31 percent) that accompany the intracarotid administration of phenylethylamine (2 X 10(-6) moles per kilogram per minute) were unaffected by the prior administration of either phenoxybenzamine (1.5 mg per kilogram, IV) or pimozide (0.5 mg per kilogram, IV). The administration of phenoxybenzamine and pimozide per se did not significantly disturb cerebral blood flow or oxygen consumption. The ability of migraine patients to oxidatively deaminate phenylethylamine is reduced at the time of their attacks. In the present experiments, the administration of the monoamine oxidase type B inhibitor, deprenyl (1 mg per kilogram, IV), did not effect significant changes in cerebral blood flow or cerebral oxygen consumption. However, following deprenyl, the administration of phenylethylamine (4 X 10(-8) moles per kilogram per minute), a concentration which was without effect in normal animals, significantly reduced cerebral blood flow. Some of the possible mechanisms influencing the sensitivity of the cerebral circulation to phenylethylamine, and their relationship to migraine, are considered.
Animals↗
Cerebral circulatory and metabolic effects of vasoactive intestinal polypeptide [proceedings].
Explore the source record for details and available documents.
Animals↗
Indirect sympathomimetic agents and cerebral blood flow and metabolism.
The effects upon cerebral blood flow (CBF) and oxygen consumption (CMRO2) of the infusion into the internal carotid artery of tyramine and amphetamine were investigated in 24 anaesthetized baboons. The infusion of tyramine was without effect upon CBF and CMRO2 at normocapnia, even at concentrations which significantly raised arterial blood pressure. However, marked reductions in cerebral blood flow were noted at hypercapnia during the infusion of tyramine (2.5 X 10(-7) moles/kg/min). The infusion of amphetamine (7.5 X 10(-10) moles/kg/min) resulted in significant increases in CBF (32%) and CMRO2 (37%). However, an increased concentration of amphetamine (2.5 X 10(-7) moles/kg/min) significantly reduced CBF (22%) and CMRO2 (20%). It is suggested that amphetamine, by virtue of being able to cross the blood--brain barrier and interact with the cerebral monoamine systems, is able to influence cerebral blood flow by inducing changes in cerebral metabolism, and that the minimal reactivity of the cerebral circulation to the infusion of tyramine is the result of the inability of tyramine to cross the blood--brain barrier.
Animals↗
Effects of dopaminergic agonists and antagonists on isolated cerebral blood vessels.
The vasomotor response of dopamine and dopaminergic agonists was studied in vitro on middle cerebral arteries from cat and pial arteries from humans. The action of various inhibitors was tested in order to define the receptors involved. A contractile response could be obtained by epinine, apomorphine and dopamine in the mentioned order of potency. The effect was blocked by alpha-receptor as well as serotonin receptor antagonists. The mode of inhibition suggested that serotonin receptors rather than alpha-adrenoceptors mediated the dopamine-induced contraction. A dose-dependent dilatation could be evoked by the dopaminergic agonists on actively contracted pial arteries. The relative potency was epinine greater than dopamine greater than apomorphine. The order of potency for the agonists, together with blocking experiments (including a parallel shift in the log dose-response curve induced by bulbocapnine), indicated that the vasodilatation is mediated by specific dopamine receptors.
Animals↗
Vasomotor response of cerebral blood vessels to dopamine and dopaminergic agonists.
The vasomotor response of dopamine and dopaminergic agonists was studies on feline isolated middle cerebral arteries in vitro and pial arterioles in situ following microapplication. The action of various inhibitors was tested to define the receptors involved. The contractile response could be blocked by alpha-receptor as well as serotonin receptor antagonists. The mode of inhibition suggested that serotonin receptors rather than alpha-adrenoceptors mediated the dopamine-induced contraction. A dose-dependent dilation could be evoked by the dopaminergic agonists on actively contracting pial arteries in vitro and by apomorphine in situ. The relative potency for the agonists together with blocking experiments indicated that the vasodilation was mediated by specific dopamine receptors.
Animals↗
Migraine and the blood-brain barrier.
The prodromal (cerebral) symptoms of migraine are associated with a fall in cerebral blood-flow (C.B.F.). The suggestion that various circulating vasoactive agents might be the cause of this fall in C.B.F. ignores the contradictory findings that the cerebral vascular bed is normally unresponsive to such agents; but if the blood-barrier is disrupted, systemically administered monoamines and prostaglandins elicit pronounced changes in cerebral-tissue perfusion and metabolism. A defect in the blood-brain barrier of migraine patients (particularly those in whom an item of diet may trigger an attack) would make the cerebral circulation vulnerable to variations in circulating levels of vasoactive substances. Alternatively, the barrier could be intact in non-dietary patients, but release of monoamines or prostaglandins from the brain itself could account for the observed changes in the cerebral circulation.
Blood-Brain Barrier↗
Cerebral circulatory and metabolism changes following amphetamine administration.
Explore the source record for details and available documents.
Amphetamine↗
Cerebral circulation: effect of stimulation and blockade of dopamine receptors.
The effects of stimulation and blockade of dopaminergic receptors on cerebral blood flow and metabolism were investigated in 15 anesthetized baboons. The intravenous administration of apomorphine resulted in immediate, dose-dependent increases in cerebral blood flow (increased by 58% following 0.1 mg/kg apomorphine) which were always accompanied by increases in cerebral oxygen consumption (increased by 36% with 0.1 mg/kg) and glucose uptake (increased by 72% with 0.1 mg/kg). It is suggested that the primary action of apomorphine is on cerebral metabolism and secondarily on cerebral blood flow rather than directly on cerebral vascular smooth muscle. Pimozide, at doses that totally blocked apomorphine-induced increases, was without effect on cerebral blood flow and metabolism. The dilatatory response of the cerebral circulation to hypercapnia was preserved during dopamine-receptor blockade. The basal level of overall cerebral metabolism and hemispheric cerebral blood flow does not appear to be dependent to any large extent on the activity of the dopaminergic pathways in the central nervous system.
Animals↗
Phenylethylamine and cerebral blood flow. Possible involvement of phenylethylamine in migraine.
Phenylethylamine can initiate migraine-type headaches in susceptible individuals. Migraine sufferers have a reduced ability to deaminate all monoamines, but particularly phenylethylamine. Phenylethylamine readily crosses the blood-brain barrier and thus could be a mediator of the cerebrovascular disturbances seen in migraine attacks. Cerebral blood flow was measured in 15 anesthetized baboons by the intracarotid 133Xe clearance technique. Phenylethylamine (4 x 10(-7) moles.kg-1min-1) produced significant increases in cerebral blood flow (36 percent) and cerebral oxygen consumption (45 percent) during the first 40 minutes of infusion. In contrast, an increased phenylethylamine concentration (2 X 10(-6) moles.kg-1min-1) constricted the cerebral bed (cerebral blood flow reduced by 28 percent). The response of the cerebral circulation to hypercapnia was preserved during the infusion. Phenylethylamine thus is capable of producing in an experimental animal a pattern of cerebrovascular events similar to those seen in migraine.
Animals↗
The effect of norepinephrine on the spinal cord circulation and its possible implications in the pathogenesis of acute spinal trauma.
The effect of intra-arterially administered norepinephrine (NE) upon spinal cord blood flow (SCBF), before and after disruption of the blood-cord barrier was studied in dogs. Barrier disruption was accomplished with an intra-arterial bolus injection of 2.5 M urea. Multiple ligations of branches of the posterior aorta and cannula placements ensured that the urea was directed to the lumbar and sacral segments of the cord. The SCBF was measured by the hydrogen clearance method. Intra-arterial urea by itself had no significant effect on SCBF. The intra-arterial infusion of NE (12 microgram/min and 30 microgram/min) was without overall effect on SCBF. However, if the blood-cord barrier had been previously disrupted with hypertonic urea, both concentrations of NE resulted in large reductions in SCBF. No such reductions in SCBF were seen with blood-cord barrier disruption and NE if the animals had been pre-treated with the alpha-blocker, phenoxybenzamine (1.5 mg/kg). Some aspects of the possible involvement of NE in the pathophysiology of acute spinal injury are discussed.
Animals↗