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Biomedical subjects

M O Carruba

Publications and source records attributed to M O Carruba.

At least 73 records · Page 4Linked to original sources
PubMed1985

Tolerance to some behavioural effects of lisuride, a dopamine receptor agonist, and reverse tolerance to others, after repeated administration.

To investigate whether prolonged pretreatment with the dopamine (DA) agonist lisuride would result in modification of some of its behavioural effects, food intake, locomotor activity, body temperature or stereotyped and mounting behaviour were evaluated after acute injections of different doses of lisuride into rats, pretreated daily for four weeks with either saline or lisuride. Rats pretreated with lisuride developed tolerance to its anorexigenic and hypothermic effects, and reverse tolerance to its effects on locomotor activity, stereotyped and mounting behaviour. Pretreatment with lisuride did not modify the activity of drug-metabolizing enzymes in the liver. These results, in addition to revealing the pattern of the changes in the behavioural effects of a DA agonist drug, after repeated administration, may be taken as evidence for the existence of different DA receptor systems in different areas of the brain, that mediate different behavioural effects, and that differ markedly in their reactions to prolonged stimulation with an agonist drug.

Animals↗
PubMed1983

Effects of neurochemical lesions restricted to spinal cord monoaminergic neurons on blood pressure and sympathetic activity of spontaneously hypertensive rats.

Intraspinal (i.s.) injection of 6-hydroxydopamine or 5,7-dihydroxytryptamine in newborn spontaneously hypertensive rats (SHR) resulted, in the adult animal (30-week-old), in a marked decrease of spinal cord noradrenaline (NA) or 5-hydroxytryptamine (5-HT) levels, respectively. Since both neurotoxin- and vehicle-injected rats developed full hypertension and had similar plasma catecholamine concentrations, it is concluded that in SHR neither spinal cord NA nor 5-HT play a major role in development and maintenance of hypertension.

Animals↗
PubMed1983

Effects of antihypertensive drugs on sexual behaviour of male rats.

Equiactive antihypertensive doses of clonidine, alpha-methyldopa, hydralazine, propranolol and of a novel compound 355-1057 were tested in an experimental model in which sexual activity was stimulated pharmacologically by lisuride. It was found that those antihypertensive drugs known to cause disturbances in sexual function in men, i.e., clonidine, alpha-methyldopa, hydralazine and propranolol, inhibited lisuride-induced mounting behaviour in male rats, as measured by a decrease in the percentage of animals mounting or in the number of mounts per active animal. The novel antihypertensive compound 355-1057, that seemed in preliminary clinical trials to be devoid of sexual side-effects in men, had no significant effect on the mounting behaviour. It seems, therefore, that the present experimental model could be predictive for antihypertensive drug-induced sexual side-effects in man.

Animals↗
PubMed1982

Plasma catecholamine concentrations in normotensive rats of different strains and in spontaneously hypertensive rats under basal conditions and during cold exposure.

Under basal conditions, the levels of circulating norepinephrine (NE) and epinephrine (E) were higher in normotensive Wistar rats of different origins than in Sprague-Dawley rats. Since the decline of 3H-NE concentration in the plasma after i.v. injection was similar in Wistar and in Sprague-Dawley rats, the higher levels of endogenous NE in the former strain probably reflect greater NE release from sympathetic nerve terminals. In normotensive Sprague-Dawley and Wistar rats, plasma NE rose to various extents during cold exposure (4 degrees C), depending on the basal plasma NE levels. Compared with normotensive Wistar Kyoto rats (WKY), spontaneously hypertensive rats (SHR) had similar basal plasma E and NE concentrations, similar rates of 3H-NE disappearance, but more rapid increases to higher values of plasma NE during cold exposure. It is concluded that the basal rate of peripheral catecholamine release does not seem to be the main determining factor for arterial blood pressure in the various rat strains and that the sympathetic neuronal system of SHR is more responsive to cold exposure than that of WKY rats.

Animals↗
PubMed1982

Effects of GTP and sodium on rat striatal dopamine receptors labeled with lisuride.

[3H]Lisuride binding to rat striatal membranes appeared to be stereospecifically displaced by the dopamine antagonist butaclamol. Sodium increased the number of [3H]lisuride binding sites (Bmax) without changing the dissociation constant (Kd). GTP did not affect [3H]lisuride binding characteristics, either with or without sodium. These results suggest that dopamine receptor sites labeled by lisuride are at least in part sodium-dependent, possibly the D2-receptors not involved in adenylate cyclase stimulation.

Animals↗
PubMed1982

Plasma adrenaline and noradrenaline concentrations in diabetic patients with and without autonomic neuropathy at rest and during sympathetic stimulation.

Plasma concentrations of adrenaline and noradrenaline were measured radio-enzymatically in nine patients with diabetic autonomic neuropathy, seven diabetic patients without autonomic neuropathy and nine normal subjects, in the recumbent position and after standing. Furthermore, in six patients with autonomic neuropathy and in the normal subjects, plasma noradrenaline and adrenaline concentrations were determined during and after cyclo-ergometer exercise. No differences in plasma adrenaline concentrations were found at any time in the study. Basal plasma noradrenaline levels were significantly lower in diabetic patients with autonomic neuropathy than in the non-neuropathic diabetics or healthy control subjects. After standing, plasma noradrenaline rose to significantly higher levels in both control and diabetic subjects without neuropathy than in the patients with autonomic neuropathy. During exercise (up to 100 W load), plasma noradrenaline rose to similar levels in healthy controls and in patients with diabetic neuropathy. These data indicate that in diabetic autonomic neuropathy there is reduced peripheral neurosympathetic tone at rest but a normal response to moderate exercise. Blunted neurosympathetic responses to standing seem to be a consistent feature of diabetic autonomic neuropathy, particularly in those patients with severe postural hypotension.

Adult↗
PubMed1982

Effects of oral chlordemethyldiazepam on plasma adrenaline and noradrenaline and cardiovascular reactivity in preoperative patients.

In 11 preoperative women, plasma adrenaline (A) concentrations were lower after oral administration of an antianxiety dose (19.25 micrograms/kg) of chlordemethyldiazepam (Cl-DMDZ) than the predrug values, or those in 12 patients given placebo. No significant differences in supine plasma noradrenaline (NA), blood pressure (BP) and heart rate values were observed. Digital plethysmography showed finger vasoconstriction after placebo and vasodilatation after Cl-DMDZ. A mental arithmetic test caused equivalent rises in plasma A in both groups. Standing caused plasma NA to rise to similar levels in both groups of patients, but the BP decrease was less and there was a markedly lower incidence of orthostatic hypotension in the Cl-DMDZ treated group. It is concluded that the effect of Cl-DMDZ on the release of catecholamines from the peripheral sympathetic system consists essentially of decreasing basal adrenomedullary activity. CL-DMDZ appears to prevent the orthostatic hypotension which occurs when neurosympathetic reflex activation is normal.

Abortion, Induced↗
PubMed1981

Plasma catecholamines in rats exposed to cold: effects of ganglionic and adrenoreceptor blockade.

Exposure to cold (4 degrees C) of catheterized rats acclimated to 20 degrees C resulted in a progressive increase in plasma noradrenaline (NA) concentrations which reached values consistently more than twice the basal ones (20 degrees C) by about 30 min. No further increase in plasma NA levels were detected when the cold exposure was continued for 24 h. Plasma adrenaline (A) and dopamine levels did not change at any time studied. Adrenalectomized rats exposed to cold exhibited percent rises in plasma NA similar to those in intact rats. An increase in plasma A levels concomitant with that of NA was observed following exposure to cold of rats in which either basal catecholamine release was impaired by chlorisondamine or the vasoconstrictor response was impeded by phentolamine. Propranolol did not modify the acute neurosympathetic response to cold. Exposure to cold (4 degrees C) for short periods of time combined with the measurement of plasma catecholamines is proposed as a useful and reproducible method for studying a pure neurosympathetic response in the rat.

Adrenalectomy↗
PubMed1981

Blood sampling by chronic cannulation technique for reliable measurements of catecholamines and other hormones in plasma of conscious rats.

An optimalized technique for chronic venous and arterial cannulation of rodents that permits repeated blood collections in unstressed, freely moving animals is presented. The indwelling catheter can also be used for chronic and/or acute drug administration in rats or other small laboratory animals, as well as for the recording of blood pressure and heart rate. The attachment device of minimal size is easily fixed on the head of the animals, allowing the additional implantation of a chronic cannula for intracerebral injections. No residual effects on the resting levels of plasma catecholamines (CA) were present 24-hr after surgery and anesthesia for implanting the cannula. No variations of plasma CA concentrations were observed at the different times of day examined or as a consequence of withdrawal of subsequent blood samples. Training the animals to be handled prevented the increase in plasma prolactin levels produced by decapitation; training had no influence on the decapitation-induced rises in plasma CA concentrations.

Animals↗
PubMed1980

Anorectic effect of lisuride and other ergot derivatives in the rat.

Three ergot derivatives, lisuride, lergotrile and bromocriptine, given to rats trained to eat 4 h a day, induced a dose- and time-related anorexia. They were more potent in this context than either amphetamine or fenfluramine. Lisuride and lergotrile failed to increase locomotor activity or to induce stereotyped behaviour at doses corresponding to the ID50 on food intake. At this dose, bromocriptine slightly stimulated motor activity. The anorectic effect of the three compounds was selectively antagonized by blockers of dopamine (DA) receptors in the central nervous system but not by either inhibiton of catecholamine synthesis or blockade of alpha- or beta-adrenoceptors or of serotonergic receptors. Also two blockers of 'peripheral' DA receptors failed to antagonize ergoline-induced anorexia. These findings indicate that stimulation of DA receptors involved in feeding behaviour was responsible for the anorexigenic effect of the ergot derivatives investigated. In most instances this effect occurred at dose levels which failed to induce central stimulant effects.

Animals↗
PubMed1980

Effects of lisuride on body temperature of rats and rabbits: relation to microsomal biotransformation and dopaminergic receptor stimulation.

In rats, lisuride, either administered systemically or intracerebroventricularly induced a dose-related hypothermia. This effect was selectively antagonized by blockade of DA receptors in the CNS but not by inhibition of catecholamine synthesis or blockade of serotoninergic receptors. Also a blocker of "peripheral" DA receptors failed to antagonize the hypothermic effect of lisuride in rats. Induction of rat liver microsomal drug-metabolizing enzymes by phenobarbital counteracted lisuride-induced hypothermia. In rabbits lisuride induced a hyperthermic response which was sensitive to both pimozide and metergoline pretreatment. These findings indicate that stimulation of brain DA receptors involved in thermoregulation is responsible for the changes in body temperature indiced by lisuride in rats and rabbits and that these effects are caused by the drug itself and do not require previous biotransformation into an active metabolite.

Animals↗
PubMed1980

Enhanced behavioural, electrocortical and hyperthermic effects of serotonin-like agents after impairment of serotonin transmission in fowl brain.

In adult fowls and in young chicks (Gallus domesticus) the effects were studied on body temperature, behaviour and electrocortical activity of 5-HT and other direct or indirect serotonin agonists given into the III cerebral ventricle in conditions of prolonged impairment of serotoninergic transmission. In chicks pretreated with 5,6-dihydroxytryptamine the subsequent intraventricular injection of 5-HT produced more intense and longer-lasting hyperthermic response and behavioural and electrocortical sleep. On the other hand fenfluramine given intraventricularly in fowls pretreated with 5,6-DHT did not produce significant body temperature and behavioural changes. After 14 and 21 day treatment with methysergide the subsequent administration of 5-HT, fenfluramine and quipazine produced in fowls an hyperthermic response and behavioural sleep more marked and longer-lasting than in control animals. The present experiments show that in conditions of chronic impairment of 5-HT function there is an enhanced behavioural and body temperature response to 5-HT and drugs acting by releasing endogenous 5-HT or 5-HT agonists.

5,6-Dihydroxytryptamine↗