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Biomedical subjects

Z S Herman

Publications and source records attributed to Z S Herman.

At least 19 recordsLinked to original sources
PubMed1979

Mediation of central prostaglandin effects by serotoninergic neurons.

Ten days after administration of 5,6-dihydroxytryptamine, which causes degeneration of central serotoninergic neurons, the depressive behavioral effects of PGF2 alpha and PGE2 were evidently inhibited. Central chemical serotoninectomy abolished the hyperthermic and hypertensive effects of PGF2 alpha, but only slightly affected those of PGE2. It is concluded that serotoninergic neurons mediate the depressive behavioral action of both PGF2 alpha and PGE2. They also mediate the hyperthermic and hypertensive action of PGF2 alpha but not of PGE2. This suggests that these prostaglandins have different central modes of action.

5,6-Dihydroxytryptamine↗
PubMed1979

Central cholinergic receptor supersensitivity after long-term atropine administration.

Rats were treated with a single dose of atropine (AT) at 5 mg/kg, or every day for 14 or 31 days with the same dose of AT, 3 h after the single dose and 24 h after the last dose of chronically administered AT, 10 micrograms of ACh was injected intracerebroventricularly, and two tests were used to examine the behavior of the animals. The tremorigenic effect of oxotremorine was also measured in mice treated with 10 mg/kg of AT for 1 month. It was shown that a single dose of AT antagonized ACh-induced behavior. The long-term treatment with AT enhanced the depressive-behavior of ACh in rats and the tremorigenic effect of oxotremorine in mice. The results suggest that long-term blockade of central cholinergic receptors induces their hypersensitivity.

Acetylcholine↗
PubMed1979

Concentration of homovanillic acid and 5-hydroxyindoleacetic acid in the ventricular cerebrospinal fluid of patients with obstructive hydrocephalus.

In 12 patients with different posterior fossa tumours the concentrations of homovanillic acid (HVA) and of 5-hydroxyindoleacetic acid (5-HIAA) were measured in cerebrospinal fluid from the lateral ventricles. All patients had obstructive hydrocephalus. Patients with a clear increase of 5-HIAA/HVA ratio in the ventricular CSF have died subsequently. This feature may have a diagnostic value, and indicates the prevalence of serotoninergic neurones in patients with obstructive hydrocephalus with fatal course after surgery.

Adult↗
PubMed1979

The influence of 6-hydroxydopamine and 6-hydroxydopa on the phospholipids content in the brain of rats.

6-hydroxydopamine and 6-hydroxydopa injected intraperitoneally in dose of 50 microgram/g in newborn rats, two and six weeks old caused a drop in content of phosphatidylcholine and phosphatidylserine, and an increase in content of phosphatidylinositol in the brains of two weeks old rats treated with 6-hydroxydopamine in comparison with controls. 6-hydroxydopa administration caused an increase of the content of phosphatidylcholine and phosphatidylinositol and decrease of diphosphatidylglycerol in the brain of two weeks old rats. In the brains of six weeks old rats only a decrease in content of phosphatidic acid was observed after administration of either 6-hydroxydopamine or 6-hydroxydopa. The results are further evidence of a nonspecific toxic action of both compounds.

Animals↗
PubMed1978

Influence of polyphloretin phosphate on the central effects of prostaglandin E2 and F2alpha in rats.

The possibility that polyphloretin phosphate (PPP) antagonizes the central effects elicited by prostaglandin (PG) E2 and F2alpha was investigated. PPP was administered i.c.v. to male Wistar rats (10 or 25 microgram) 10 or 30 min before i.c.v. injection of PGF2 or PGF2alpha (1 or 10 microgram). The duration of several component of behavior, the degree of irritability, and the rectal temperature of rats were measured; the levels of noradrenaline, dopamine, 5-hydroxytryptamine, and 5-hydroxyindoleacetic acid were measured spectrophoto-fluorometrically in discrete brain areas. PPP antagonized temperature and behaviroal changes induced in rats by PGF2alpha, but not those induced by PGE2. The magnitude of antagonism depended on the dose of PPP and on the time of the pretreatment before PGF2alpha administration. Changes in the level of biogenic amines in discrete brain areas evoked by PGs were not affected by PPP. We found that PPP antagonizes the central effects of PGF2alpha but not those of PGE2, and that changes of biogenic amines in discrete brain areas elicited by PGs are not specific.

Animals↗
PubMed1978

Model of central chemical 'serotoninectomy' in mice.

The influence of 5,7-dihydroxytryptamine (5,7-DHT) and 5,6-dihydroxytryptamine (5,6-DHT) on the level of noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) in discrete brain areas of mice was studied. Moreover, the level of free and total acetylcholine (Ach) in the whole brain was measured. The behaviour of animals was also observed. 5,7-DHT caused a relatively specific short-term decrease of 5-HT and 5-HIAA level in discrete areas of mice brain with the decrease of DA level in the striatum. This substance seems to produce a relatively specific disruption of central 5-HT neurons in mice. 5,7-DHT is an unspecific neurotoxic drug for mouse brain. Both substances did not affect the gross behaviour of mice.

5,6-Dihydroxytryptamine↗
PubMed1978

The principles of controlled clinical trials of drugs.

The principles of evaluation of new drugs are described and discussed. This evaluation is carried out in three consecutive phases. The first one is performed on young, healthy volunteers. The general response to the drug and signs of toxicity are registered. Preliminary data about absorption, elimination and metabolism are collected. The safe dosage range and preferred route of administration are settled. In the second phase, initial trials on a limited number of patients for specific disease control or prophylaxis are carried out. Patients are included in the trial by random selection and stratification. Studies are strictly controlled. To avoid bias, double-blind examination is used in paired patients, a group of patients or by the crossover design. The problems of planning, design of the study, clinical and statistical evaluation of results are discussed. Two examples of controlled clinical studies are given, concerning the assessment of antirheumatic and antianginal drugs. Finally the principles of the third phase of study are discussed. The methods of evaluation described may be applied for the assessment of entirely new substances as well as for verification of the objective therapeutic value of "old" drugs.

Angina Pectoris↗
PubMed1977

Influence of dibutyryl cyclic AMP on the level of catecholamines and 5-hydroxytryptamine in discrete areas of rat brain.

Dibutyrul cyclic AMP (dbcAMP) was injected intracerebroventricularly into rats in doses of 50, 100 or 200 microgram. Noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5-HT) or 5-hydroxy indoleacetic acid (5-HIAA) concentrations were measured spectrophotofluorimetrically in discrete brain areas: cortex, hypothalamus, striatum, hippocampus with nucleus amygdala and nucleus accumbens (limbic system) and pons with medulla oblongata. DbcAMP (in each dosage administered) decreased, NA content of cortex and of pons with medulla oblongata. NA content in the hypothalamus and striatum was decreased only after the largest dose of dbcAMP. In the limbic system NA concentration was diminished after a dose of 100 or 200 microgram of dbcAMP. There was a decrease in DA level measured in the striatum alone after a dose of 100 microgram of dbcAMP. 5-HT concentration was increased in the striatum and the pons with medulla oblongata after each dose level of dbcAMP; in the cortex after a dose of 50 and 100 microgram; and in the hypothalamus after a dose of 200 microgram. 5-HIAA level was increased in the striatum, limbic system, pons with medulla oblongata after all doses of dbcAMP. We conclude that dbcAMP affects presynaptic central catecholaminergic and serotoninergic neurons in an opposite, manner, although discrete brain areas have a different susceptibility to dbcAMP action. These findings provide some explanation for the behavioural effects of dbcAMP.

Animals↗
PubMed1977

Behavior of rats in various stages of the sexual cycle after injection of noradrenaline into the lateral ventricle of the brain.

The influence of intraventricular injection of 50 microng of noradrenaline (NA) on behavior of female Wistar rats in various phases of the sexual cycle, and the influence of 17-beta-estradiol and progesterone in castrated female rats were studied. Changes in motor and exploratory activity were observed in the course of the sexual cycle in female rats. Sensitivity to NA injected intraventricular varied significantly in different phases of the sexual cycle. Castration depressed the action of NA on motor and exploratory activities in rats, and progesterone prevented the depressive effect of NA in castrated rats.

Animals↗
PubMed1977

The central action of gamma-aminobutyric acid in rats.

The influence of 100--600 microng of gamma-aminobutyric acid (GABA) injected into the right lateral ventricle of the brain on behavior and activity of the cerebral cholinergic system was studied in Wistar rats. Proportionally to dosage, GABA inhibited motor and exploratory activity in the rats. Reduction in the content of acetylcholine in the pons and medulla oblongata was accompanied by increased acetylcholinesterase (AChE) activity. GABA changed AChE activity differently in various parts of the brain. GABA depressed motor and exploratory activity in rats in a degree dependent on its dosage and inborn exploratory of the rats, and this effect was accompanied by changes in the cerebral cholinergic system.

Acetylcholine↗
PubMed1976

Influence of 6-hydroxydopamine on the behavioral effects induced by apomorphine or clonidine in rats.

The aim of this paper is to examine if central chemical sympathectomy induced by two injections of 6-hydroxydopamine (6-OHDA) in a dose of 250 mug intracerebroventricularly (i.c.v.) affects behavioral phenomena elicited by apomorphine (AP) (1 or 1.2 mg/kg i.p.) or clonidine (CL) (0.1 MG/KG, 5 Or 1 mug/kg i.p.). Experiments were carried out on male Wistar rats. The time of duration of several components of behavior and the degree of irritability of rats were measured. Moreover, open field and hole test were performed. The lower dose of AP did not affected behavior of rats. The higher dose increased the locomotor and exploratory activity of animals. 6-OHDA potentiated these effects of AP. CL (0.1 mg/kg) had a depressive effect on the rats' behavior, which was potentiated by 6-OHDA. CL (5 mug/kg) had no effect on the rats' behavior, but in a dose of 1 mug/kg caused excitatory behavior. This type of behavior was abolished by 6-OHDA. In conclusion, central chemical sympathectomy caused increased sensitivity of the central nervous system on AP. Excitatory behavioral effects of CL in low dosage may be connected with stimulation of central adrenergic receptors. Depressive behavioral effect of CL in high dosage is unspecific. Central chemical sympathectomy affects by different methods the reactivity of dopaminergic and noradrenergic neurons.

Animals↗
PubMed1976

Central effects of prostaglandins F2alpha and E1.

In male Wistar rats PGF2alpha or PGE1 were injected intracerebroventricularly (icv) in a dose of 1 or 10 mug. Immediately or 1 hr after injection the locomotor and exploratory activity were measured. The levels of noradrenaline (NA), dopamine (DA) 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and acetylcholine (Ach) were measured in discrete brain areas. Both PGs applied ivc caused the depression of locomotor and exploratory activity in rats. PGE1 acted longer. Both substances but PGE1 more intensively affected the level of estimated biogenic amines in different brain structures. It is concluded that PGF2alpha and E1 are central nervous depressants. Both PGs affect neurons producing NA or 5-HT or Ach in discrete areas of brain in different manner. There is different susceptibility of brain structures on PGs action.

Acetylcholine↗
PubMed1976

Behavioural effects of dopamine and 5-hydroxytryptamine in centrally chemosympathectomized rats.

In rats central chemical sympathectomy (CCS) was elicited by intracerebro-ventricular (icv) injection of two doses of 250 mug of 6-hydroxydopamine (6-OHDA) at 48 hr interval. 7 days after the last injection when full CCS is developed, 10 mug of dopamine (DA) or 5-hydroxytryptamine (5-HT) were applied icv and locomotor and exploratory activity and irritability of animals were measured. CCS reversed the depressive effect of DA on the locomotor and exploratory activity, and intensified irribability of animals. It intensified the effect of 5-HT on the exploratory activity without changing the others observed behavioral parameters. It is concluded that CCS changes reactivity of central nervous system of pharmacological effects of DA and slightly affects the central response to 5-HT.

Animals↗
PubMed1976

Behavioral effects of withdrawal of fluphenazine after long-term treatment.

Male Wistar rats were treated i.p. with 10-(3-[4-(2-hydroxyethyl)-1-piperazinyl]-propyl)-2-(trifluoromethyl)-phenothiazine (fluphenazine dihydrochloride, FL, Mirenil) in a dose of 1 mg/kg for 28 weeks, or in a dose of 5 mg/kg for 21 weeks, beginning from the 6th day of life. Withdrawal of the drug caused an abstinence syndrome in the form of increased locomotor and exploratory activity and increased irritability of the animals. Behavioral observation during the period of drug administration indicated the development of tolerance to behavioral effects of FL. Male and female Wistar rats from mothers treated i.p. with 1 mg/kg of FL during pregnancy and lactation period were treated for 32 weeks with 1 mg/kg of FL beginning from the 8th day of life. In males, during the period of withdrawal as well as during renewed treatment, an increase in locomotor and exploratory activity was observed. The behavior of female rats during the withdrawal period was similar to that of control animals. The abstinence syndrome observed after withdrawal of FL is modified by the time of life at which treatment was started and by the sex of the animals.

Age Factors↗