TRH dissociates the aggressivity of vegetative and motor phenomena induced by carbachol in the cat

In these experiments interaction of thyrotropin releasing hormone (TRH) and carbachol injected into the cerebral ventricles of unanaesthetized cats has been investigated. Intracerebroventricular (i.c.v.) carbachol as well as i.c.v. TRH produced emotional behaviour, autonomic and motor phenomena. The most impressive feature of i.c.v. carbachol was the aggressive behaviour, whereas that of i.c.v. TRH the autonomic changes. In cats treated with i.c.v. TRH, the aggressive behaviour, but the autonomic and motor changes of i.c.v. carbachol was potentiated. Since there is evidence that carbachol acts mainly on muscarinic M-2 receptors, the potentiation by TRH of aggressive behaviour, but not the autonomic and motor changes induced by carbachol could indicate heterogeneity of central muscarinic M-2 receptors.     

Medullary kappa hyperalgesic mechanisms II. The effects of ethylketazocine administered into the fourth cerebral ventricle of the conscious dog

Ethylketazocine (EKC) (2 micrograms/100 microliter/min for 15 min) was infused into the fourth cerebral ventricles of conscious dogs. The drug produced hyperalgesia, respiratory depression, miosis, increased EEG electrogenesis and behavioral sedation. Hyperthermia and tremulousness were observed in some animals. These pharmacologic effects reflect the action of EKC on pontomedullary periventricular sites which control nociception, autonomic function and arousal.     

Psychomotor excitation caused by beta-endorphin: effect of rubidium and lithium

Effects of lithium and rubidium administered into the cerebral ventricles of conscious cats on psychomotor excitation produced by synthetic human beta-endorphin similarly injected have been investigated. Lithium, but not rubidium, prevented the psychomotor stimulation caused by beta-endorphin. Naloxone, applied intracerebroventricularly, also prevented the psychomotor stimulation produced by this polypeptide. It appears, therefore, that only lithium has a psychotherapeutic value when homeostatic neurohumoral mechanisms are disturbed in the central nervous system by a surplus of beta-endorphin.     

Metabolism of (1-14C)-palmitic acid in the cat's brain]

Following injection into the cerebral ventricles of conscious cats, (1-14C) palmitic acid was rapidly taken up and incorporated into a variety of brain lipids. The peak of uptake of (1-14C) palmitic acid, about 50% of injected radioactive material, into the brain tissue was obtained within the first 24 h following its administration. Thereafter, the radioactivity slowly decreased reaching the least value by the end of the second week. The most heavily labelled lipids were the phospholipids, while the free fatty acids were appreciably labelled. Small percentage of the radioactive material was found in monoglycerides, diglycerides and triglycerides. The least incorporation was into cholesterol esters.     

Distribution of 1-14C palmitic acid in brain tissue after intraventricular injection in the conscious cat]

The distribution of (1-14C) palmitic acid in the brain tissue following the injection into the cerebral ventricles of conscious cats was investigated. The radioactive material was found in the brain tissue surrounding the cerebral ventricles and in the cerebral cortex, but in varying amounts : the smallest amounts were found in the cerebral cortex, while the highest in the thalamus and in the hippocampus. Radioactive material was also found in the peripheral venous blood. The amount of the radioactive material in the grey matter lining the cerebral ventricles as well as in the cerebral cortex was time-dependant. The labelled material in the structures surrounding the cerebral ventricles and in the cerebral cortex increased within first four hours after its intraventricular administration. Thereafter, throughout subsequent 48 hours either it slowly disappeared in the caudate nucleus and in the thalamus, or it was retained in the hypothalamus and in the floor of the IV ventricle.     

Nitric oxide-mediated central sympathetic excitation promotes CNS and pulmonary O2 toxicity

In hyperbaric oxygen (HBO(2)) at or above 3 atmospheres absolute (ATA), autonomic pathways link central nervous system (CNS) oxygen toxicity to pulmonary damage, possibly through a paradoxical and poorly characterized relationship between central nitric oxide production and sympathetic outflow. To investigate this possibility, we assessed sympathetic discharges, catecholamine release, cardiopulmonary hemodynamics, and lung damage in rats exposed to oxygen at 5 or 6 ATA. Before HBO(2) exposure, either a selective inhibitor of neuronal nitric oxide synthase (NOS) or a nonselective NOS inhibitor was injected directly into the cerebral ventricles to minimize effects on the lung, heart, and peripheral circulation. Experiments were performed on both anesthetized and conscious rats to differentiate responses to HBO(2) from the effects of anesthesia. EEG spikes, markers of CNS toxicity in anesthetized animals, were approximately four times as likely to develop in control rats than in animals with central NOS inhibition. In inhibitor-treated animals, autonomic discharges, cardiovascular pressures, catecholamine release, and cerebral blood flow all remained below baseline throughout exposure to HBO(2). In control animals, however, initial declines in these parameters were followed by significant increases above their baselines. In awake animals, central NOS inhibition significantly decreased the incidence of clonic-tonic convulsions or delayed their onset, compared with controls. The novel findings of this study are that NO produced by nNOS in the periventricular regions of the brain plays a critical role in the events leading to both CNS toxicity in HBO(2) and to the associated sympathetic hyperactivation involved in pulmonary injury.     

Nature of hypo- and hyperthermia induced by the calcium antagonist nicardipine

The effects of nicardipine, a calcium channel blocking agent, injected into the cerebral ventricles, (i.c.v.), on the body temperature of unanaesthetized cats have been investigated. Nicardipine produced a biphasic effect on body temperature: a transient dose-dependent decline followed by a longlasting elevation. The fall, but not the rise, of body temperature was associated with a dose-dependent increase in respiration. Yohimbine, in small doses, but not prazosin and propranolol, when injected into the cerebral ventricles, attenuated the hypothermia evoked by i.c.v. nicardipine. However, all the antagonists, except yohimbine in large doses, depressed the hyperventilation induced by nicardipine. Calcium chloride (i.c.v.) reversed, while i.c.v. methysergide virtually had no effect on hyperthermia caused by i.c.v. nicardipine. Nicardipine virtually had no effect on body temperature of intracerebroventricular reserpine- and alpha-methyl-p-tyrosine-treated cats. It appears, therefore, that nicardipine at least in part evoked hypothermia through alpha-2 adrenoceptors located presynaptically, while nicardipine-induced respiratory changes are mediated also partly via alpha-adrenoceptors having mixed alpha 1 and alpha 2 properties. The hyperthermic effect of nicardipine, on the contrary, is mainly due to an action on voltage-dependent calcium ion channels. The contribution of the hyperventilation to the hypothermic effect of nicardipine cannot be of great importance, since the hypothermia was accompanied with hypoventilation when alpha- and beta-adrenoceptor blocking agents were used.     

Effect of nicergoline and dihydroergotamine, injected into the cerebral ventricles, on arterial pressure in the cat

Nicergoline, injected into the cerebral ventricles of anaesthetized cats induced a moderate, but longlasting and dose-dependent fall of the blood pressure. Dihydroergotamine, in moderate doses, had no effect on the arterial blood pressure. Toxic doses of nicergoline and dihydroergotamine provoked a pronounced fall of the arterial blood pressure and inhibition of the respiration. Bradycardia only appeared after toxic doses of dihydroergotamine. It is concluded that the hypotensive effect of nicergoline is at least in part central in origin.     

beta-Endorphin-induced hyperthermia in the cat

beta-Endorphin was injected into the third cerebral ventricle (ICV) of conscious, unrestrained cats. Hyperthermic response to 50 microgram of this peptide were reduced by 20-100 microgram naloxone given ICV 1 hr later. A dose of 40 microgram beta-endorphin increased body temperature at ambient temperature of 4, 22 and 34 degrees C, with the response being greater the warmer the environment. These results indicate that beta-endorphin acts on a central naloxone-sensitive receptor which is probably the v2 receptor that is activated by low doses of D-Ala2-Met-enkephalinamide to evoke a similar pattern of change in body temperature over a comparable range of ambient temperatures.     

Effects of nifedipine and verapamil on body temperature in cats

Nifedipine and verapamil injected into the cerebral ventricles of unanaesthetized cats produced a longlasting rise in the body temperature. The hyperthermic effect of nifedipine and verapamil were not dose-dependent. The hyperthermic effect of verapamil was preceded by a shortlasting fall in the body temperature, which was not dose-dependent. Calcium antagonists, nifedipine and verapamil also produced mydriasis, tachypnoea, dyspnoea, ataxia, tremor and muscular weakness. These symptoms were inconsistent and of slight intensity. In agreement with the theory of ionic set point controlling the body temperature, the most probable explanation is that calcium antagonists, nifedipine and verapamil produced changes in the body temperature by acting on sodium and calcium fluxes in the posterior hypothalamus.     

2-Deoxy-D-glucose inhibition of prostaglandin E1 hyperthermia and yeast fever in mice.

2-Deoxy-D-glucose (2-DG) and sodium salicylate were evaluated relative to their effects on body temperature in mice with prostaglandin E1 (PGE1)hyperthermia or yeast fever. Injection of 2-DG into the cerebral ventricles of conscious mice abolished the hyperthermia of PGE1 and reduced the fever produced by yeast, while sodium salicylate was effective only in yeast fever. The data are suggestive of glucose dependency of thermoregulatory centers in the brain.     

Effects of Intracisternally Injected Serotonin on Cerebral Blood Flow in Cats During Winter and Summer,and After Dark Exposure

This investigation reports on two experiments: (a) The examination of the effects of intracisternally injected serotonin on cerebral blood flow and systemic pressure in cats during winter (1/10–3/7) and summer (7/6–9/3) at a latitude of 39' 40, and (b) the effects of similarly injected serotonin on the same parameters in 11 cats after exposure to 3 days of continuous darkness during the summer months. Serotonin (5 mg) injected intracisternally produced significant decreases in cerebral blood flow and systemic pressure that lasted from 60 to 180 min after injection. Blood flow decreases, expressed as percentage change from baseline, seen during winter (n = 24) periods were significantly greater [analysis of variance (ANOVA), p < 0.02] from decreases seen during summer (n = 25) periods. Following serotonin injection, systemic pressure decreases between the winter and summer cats were not significantly different. Eleven summer cats were subjected to 3 days of continuous darkness before being injected with serotonin. Blood flow decreases in the dark-exposed cats were significantly (p < 0.05) greater than those seen in normal light-exposed cats, whereas systemic pressure changes were not different. These studies suggest that the seasonal photoperiod may affect the sensitivity of cerebral vessels to intracisternally injected serotonin in cats.     

Sildenafil acts on the central nervous system increasing sympathetic activity.

Sildenafil induces vasodilation and is used for treating erectile dysfunction. Although its influence on resting heart function appears to be minimal, recent studies suggest that sildenafil can increase sympathetic activity. We therefore tested whether sildenafil injected into the central nervous system alters the autonomic control of the cardiovascular system in conscious rats. The effect of sildenafil citrate injected into the lateral cerebral ventricle was evaluated in conscious rats by means of the recording of lumbar sympathetic nerve activity (LSNA), spectral analysis of systolic arterial pressure and heart rate variability, spontaneous baroreflex sensitivity, and baroreflex control of LSNA. Intracerebroventricular (ICV, 100 microg /5 microl) administration of sildenafil caused remarkable tachycardia without significant change in basal arterial pressure and was associated with a conspicuous increase (47 +/- 14%) in LSNA. Spectral analysis demonstrated that systolic arterial pressure oscillations in the low frequency (LF) range were increased (from 6.3 +/- 1.5 to 12.8 +/- 3.8 mmHg(2)), whereas the high frequency (HF) range was not affected by ICV administration of sildenafil. Sildenafil increased pulse interval oscillations at LF and decreased them at HF. The LF-HF ratio increased from 0.04 +/- 0.01 to 0.17 +/- 0.06. Spontaneous baroreflex sensitivity measured by the sequence method and the baroreflex relationship between mean arterial pressure and LSNA were not affected by ICV administration of sildenafil. In conclusion, sildenafil elicited an increase in sympathetic nerve activity that is not baroreflex mediated, suggesting that this drug is able to elicit an autonomic imbalance of central origin. This finding may have implications for understanding the cardiovascular outcomes associated with the clinical use of this drug.     

Brain abnormalities induced by murine cytomegalovirus injected into the cerebral ventricles of mouse embryos exo utero

Murine cytomegalovirus (MCMV) was injected into the cerebral ventricle of mouse embryos on day 13 of gestation after exposing the embryos out of the uterus in the abdominal cavity of the mother. The embryos were allowed to develop to day 18 of gestation, then taken out from the abdominal cavity. Macroscopically, there were four expanded and three distorted brains out of 19 surviving embryos, whereas no brain abnormality was noticed in 13 embryos injected with culture medium instead of MCMV in the same way. Histopathological examination showed hydrocephalic lesions with strong dilatation of the ventricles and atrophy of the cerebral cortex, and inflammatory lesions with granulomatous proliferation of the ventricular walls with disappearance of the cortical zonation. Immunohistochemically, MCMV-induced nuclear antigen-positive cells were frequently observed in the wall of the ventricles and occasionally scattered in the cerebral cortex, white matter, and the nucleus basalis. Some fetuses injected with MCMV in the same way were recovered from the abdominal cavities on day 18 of gestation and transferred to foster nurse mothers. They showed massive cerebral necrosis after feeding for 9 days after birth. Brain abnormalities of mouse embryos after intraventricular injection with MCMV may provide an experimental model of brain damage induced by congenital cytomegalovirus infection.     

Morphological changes in the central canal of the cat after kaolin injection into the cisterna magna

40 adult cats were made hydrocephalic by intracisternal injection of 200 mg Kaolin. 34 survived between 24 hours to 4 months. In 19 cases a ventriculostomy was carried out, whereby in 13 animals a contrast filling of the central canal occurred. The contrast medium injected into the ventricles entered the external CSF-space in the lumbo-sacral junction of the filum terminale. Light- and electron-microscopic studies showed adaptive structural changes of the central canal epithelium in the early stages. In later stages massive destructions of ependyma and spinal cord parenchyma were found.     

Antipyretic effect of centrally administered CRF

CRF injected into the third cerebral ventricle (0.5-2.5 micrograms) caused dose-related reductions in fever induced in rabbits by IV administration of leukocytic pyrogen. Control injections of CRF when the same animals were afebrile did not alter normal body temperature. Intravenous injections of 5 and 20 micrograms CRF, doses known to release ACTH and corticosteroids into the bloodstream in other species, did not reduce fever. CRF injected into the cerebral ventricles may be antipyretic per se, or it may reduce fever by virtue of central release of the antipyretic peptides ACTH and alpha-MSH.     

Adrenocorticotropic Hormone,Glucose and Displacement Activities in Pigeons

The possibility that displacement activities might be consequences of stress-induced humoral responses was investigated. Adrenocorticotropic hormone and glucose were injected into the brain ventricles of unrestrained domestic pigeons. ACTH leads to an increased frequency of yawning and headshaking and glucose to a decrease in arousal. It is concluded that these behavioural responses correspond partly with the displacement activities shown by birds. The role of the cerebrospinal fluid as a mediator of behaviourally active substances is discussed.     

Effect of the autonomic nervous system on the resistance of heart ventricles to fibrillation

Effects of vagus stimulation and cutting on the tolerance of heart ventricles to fibrillation in cats have been studied. The parasympathetic effects increased the tolerance of heart ventricles to fibrillation while sympathetic ones--decreased it.     

Prevention of cerebrovascular disorders with adrenergic substances]

The author suggests an experimental model of cerebrovascular disorders of the neurogenic (adrenergic) nature following the administration of KCl into the lateral ventricles of the brain of cats or dogs. Surgical desympathization considerably reduced the spasms of the cerebral vessels caused by the central effect of KCl. Dihydroergotoxin, phenoxybenzamine, tropaphene, guanethidine and nialamide produced both the therapeutic and the prophylactic influence under the mentioned experimental disorders of the cerebral circulation.     

Potent osmoregulatory actions of homologous adrenomedullins administered peripherally and centrally in eels

The teleost adrenomedullin (AM) family consists of three groups, AM1/AM4, AM2/AM3, and AM5. In the present study, we examined the effects of homologous AM1, AM2, and AM5 on drinking and renal function after peripheral or central administration in conscious freshwater eels. AM2 and AM5, but not AM1, exhibited dose-dependent (0.01-1 nmol/kg) dipsogenic and antidiuretic effects after intra-arterial bolus injection. The antidiuretic effect was significantly correlated with the degree of associated hypotension. To avoid the potential indirect osmoregulatory effects of AM-induced hypotension, infusion of AMs was also performed at nondepressor doses. Drinking was enhanced dose-dependently at 0.1-3 pmol.kg(-1).min(-1) of AM2 and AM5, matching the potency and efficacy of angiotensin II (ANG II), the most potent dipsogenic hormone known thus far. AM2 and AM5 infusion also induced mild antidiuresis, while AM1 caused antinatriuresis. Additionally, AMs were injected into the third and fourth ventricles of conscious eels to assess their site of dipsogenic action. However, none of the AMs at 0.05-0.5 nmol induced drinking, while ANG II was highly dipsogenic. AM2 and ANG II injected into the third ventricle increased arterial pressure while AM5 decreased it in a dose-dependent manner, and both AM2 and AM5 decreased blood pressure when injected into the fourth ventricle. These data suggest that circulating AM2 and AM5 act on a target site in the brain that lacks the blood-brain barrier. Collectively, the present study showed that AM2 and AM5 are potent osmoregulatory hormones in the eel, and their actions imply involvement in seawater adaptation of this euryhaline species.