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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic administration of amphetamine to cats (twice daily, in doses increasing from 5 to 15 mg/kg over a 10-day period) elicited a number of behaviors, e.g., limb flick and abortive groom, characteristic of the action of hallucinogenic drugs and dependent on a depression of central serotonergic neurotransmission. This drug treatment produced large decreases (-40 to -60%) in central nervous system serotonin (5-HT) and its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA), when measured either 6 or 24 hr after the last amphetamine injection. The rate of limb flicking returned to a predrug level approximately 5 days after drug withdrawal, at which time 5-HT and 5-HIAA levels had returned to within 30 to 40% of base line. Both 5-HT and 5-HIAA returned to base-line levels within 14 days after drug withdrawal. Norepinephrine (NE), dopamine (DA) and DA metabolites were decreased 60 to 95% by chronic amphetamine treatment and showed little recovery within the 14 days after drug withdrawal. A second experiment examined the latency to onset of the behavioral and neurochemical changes with a constant dose of amphetamine (7.5 mg/kg, twice daily). Limb flicking was significantly increased above base-line levels following 3 days of amphetamine administration, at which time 5-HT and 5-HIAA levels were decreased 30 to 40%. NE, DA and DA metabolites were decreased approximately 50 to 90% by this treatment regimen. A third experiment examined the effects of a low dose of amphetamine (3.75 mg/kg), injected more frequently (every 6 hr for 6 days), to approximate the administration pattern in human amphetamine abuse. This treatment produced significant increases in limb flicking and abortive grooming on days 5 and 6 and resulted in 30 to 40% depletions of 5-HT and 5-HIAA. NE, DA and DA metabolites were decreased by approximately 50 to 90%. These data are discussed in relation to a role for serotonin in amphetamine psychosis and schizophrenia.
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PMID:Chronic amphetamine administration to cats: behavioral and neurochemical evidence for decreased central serotonergic function. 50 68

Screening studies are carried out of the pharmacological activity of 3,4-dihydropapaverine (DHP) and three of its newly-synthesized derivatives: 6'-iodo-DHP, 6'-bromo-DHP and 6'-iodu-DHP methiodide. All compounds studied manifest central depressive action which is manifested in general depression, potentiation of hexobarbital anaesthesia, without inducing sleep when independently applied, as well as inhibition of the spontaneous and amphetamine-induced motor activity of mice. 6'-Iodo-DHP and its methiodide manifest analgesic effect. All four compounds studied reduce the blood pressure of urethane-anaesthesized cats, but they do not change the noradrenaline and the acetylcholine effects. The hypotensive effect of the compounds is preserved even after atropinization of the cats. The compounds studied manifest no antitussive effect. DHP-derivatives eliminate the spasms in guinea-pig colon, induced by BaCl2 and nicotine, while DHP has no effect on them. 6'-Iodo-DHP methoiodide inhibits the hypertensive nicotine effect on cats. DHP and 6'-iodo-DHP methoiodide manifest vasoconstricting action upon perfusion of the blood vessels of isolated rat hind legs.
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PMID:Screening pharmacological studies of four dihydroisoquinoline derivatives. 53 51

The influence of progesterone on gestagen upon stress reactions and the metabolism of the biogenic amines, noradrenaline (NA) and serotonin (5-HT), were evaluated. For the 1st experiments, the 54 subjects ranged in age from 18 to 30 years. Of these, 19 (35%) had reported premenstrual tension, depression, or somatic complaints. After a preliminary interview the Moss Menstrual Distress Questionnarie and the Eysenck Personality Inventory were completed. Each subject was subsequently seen at Day 8 before predicted menstruation and 1 day before menstruation. At each session, blood samples were taken for progesterone assay. The patients sat in a darkened room and were asked to memorize words heard from a tape recording while being given a mild electric shock. The morning after the session, subjects completed the Scale of Well-Being. Psychic difficulty shortly before menstruation was higher in 49 subjects; in 16.3% of these it was severe. Only 10.2% had a negative effect. There was a correlation between the different tests. Only in the medroxyprogesterone-treated group was there a significantly higher reaction to stress on Day 1 before menstruation than a week earlier. There were large individual variations. For studies of the effects of progesterone on NA metabolism, Sprague-Dawley rats which had been ovariectomized 3 weeks earlier, were given progesterone 20 mg/kg sc on 2 consecutive days. These animals were injected with tritiated NA intracisternally and underwent a stress procedure. 3 hours after the intracisternal injection, rats were killed and tritiated-NA and its metabolites estimated. Progesterone injections did not influence NA turnover or percentage distribution of tritiated-NA and its metabolites in unstressed rats but did increase 5-HT turnover. In stress-altered 5-HT metabolism an effect of progesterone was shown. Footshock also raised endogenous progesterone levels.
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PMID:Influence of progesterone on serotonin metabolism: a possible causal factor for mood changes. 56 84

Rats show an initial depression in locomotor activity in response to doses of morphine greater than 5 mg/kg during the first hour after injection which is followed by a prolonged hyperactive phase. The effect of bilateral 6-hydroxydopamine (6-OHDA) lesions to the dorsal noradrenergic bundle on this biphasic action of morphine was studied. These lesions were found to significantly potentiate the locomotor depressant effects of morphine at 10.0 and 20.0 mg/kg while leaving the subsequent stimulant action of morphine unchanged. The cataleptic action of morphine at 20.0 mg/kg as measured in a separate test was also potentiated. These lesions were found to deplete hippocampal and cortical noradrenaline (NA) to 3% and hypothalamic NA to 32% of control values and also to cause significant increases in cerebellar and spinal NA. These data suggest a role for NA in the depressant effects of morphine but not in its subsequent stimulant actions which appear to be mediated by other neurochemical systems.
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PMID:6-OHDA lesion to the dorsal noradrenergic bundle alters morphine-induced locomotor activity and catalepsy. 56 87

1. Cholinomimetic and adrenomimetic substances were tested on the chemosensitive zones of the ventral surface of the medulla oblongata using a plexiglas ring method. Tidal volume and respiratory frequency, arterial pressure and heart frequency were observed. 2. The increase of ventilation and the depression of arterial blood pressure by locally applied acetylcholine could be blocked by previous local application of atropine. It is therefore assumed that the acetylcholine receptors have muscarinic properties. 3. Nicotine in a small dose raises arterial pressure and with higher doses a drop is observed. The responses of respiration and of arterial pressure to nicotine were blocked by previous intravenous administration of hexamethonium. 4. Local application of atropine in the caudal (L) and rostral (M) chemosensitive zones reduced resting ventilation and the slope of the ventilatory response to CO2-inhalation. Physostigmine in these areas enhanced resting ventilation leaving unchanged the slope of the ventilatory response to CO2-inhalation. 5. With high concentrations of (L)-noradrenaline and (L)-adrenaline a slight increase of arterial pressure was seen while serotonin caused a drop. 6. These results together with those of Fukuda and Loeschcke (1978) suggest that a cholinergic transmission in the surface layer of the ventral medulla is a component in the respiratory and circulatory control systems.
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PMID:A cholinergic mechanism involved in the respiratory chemosensitivity of the medulla oblongata in the cat. 57 Nov 2

The effects of ouabain 5 x 10-5 M, noradrenaline 10-7 M and nifedipine 100 mug/1 on the contractile force of the isolated rat left atrium were tested and compared at varying concentrations of calcium in the Ringer solution. The effect of ouabain was small, developed slowly and almost independently of the calcium concentration. Noradrenaline, which increases Ca++ influx during excitation, caused an increase in the contractile force which was complete within 2 min. The percentage as well as the absolute increase in contractile force was pronounced at lower, but small at higher calcium concentrations. Nifedipine, which reduces Ca++ influx during excitation, caused a decrease in contractile force which was complete within 2-4 min. The nifedipine-induced depression in contractile force decreased with a rise in the calcium concentration. It is assumed that the ouabain-induced increase in contractile force in the rat, is not mediated by an increase in the magnitude of the inward calcium current, and other modes of action for the inotropic effect of glycosides are discussed.
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PMID:A comparison of the effects of ouabain, noradrenaline and nifedipine on the contractile force of the isolated rat atrium at different calcium levels. 57 54

Stimulation of cutaneous or muscle nerve as well as activation of ventral roots L6--S1 led to inhibition of vagal bradycardia evoked by noradrenaline, in unanesthetized decerebrated cats. Unnociceptive stimulation of m. gastrocnemius in unrestrained cats evoked contraction of the muscle and was followed by depression of the cardiac component of baroreceptive reflex. Propranolol had no effect on this response, while methylatropin abolished it completely.
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PMID:[Inhibition of the cardiochronotropic component of baroreceptor reflexes following activation of somatic afferents]. 58 67

The calcium-magnesium (Ca2+-Mg2+) interaction in the process of nicotine-induced release of [3H]noradrenaline ([3H]NA) from rat isolated vas deferens was studied. Increasing extracellular concentrations of Mg2+ caused a dose-dependent depression of release of [3H]NA by nicotine, and this inhibitory effect of Mg2+ was overcome by raising the concentration of CA2+. It is concluded that Mg2+ antagonizes the nicotine-induced increase in the Ca2+ influx into the adrenergic nerve terminals, and that nicotine acts on adrenergic neuronal membrane rather than intraneuronally to cause release of NA.
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PMID:The calcium-magnesium interaction in the process of release of noradrenaline by nicotine. 59 85

1. Noradrenaline, isoprenaline, and phenylephrine have been applied my microiontophoresis to neurones in the guinea pig cerebral cortex. All three compounds produced depression of neuronal firing, and all could be antagonized to some extent by phentolamine or propranolol. 2. The responses to isoprenaline were substantially reduced in size after a few applications. Noradrenaline and phenylephrine responses were partially reduced at the time of isoprenaline insensitivity, and the responses could now be blocked completely by phentolamine. 3. The results suggest that two kinds of receptors are present in the guinea pig cerebral cortex, with properties similar to alpha and beta receptors in the periphery. A single receptor with intermediate properties would not readily explain the present results. 4. The results are not consistent with the proposal that alpha receptors mediate neuronal excitation, and beta receptors inhibition in the cerebral cortex. 5. It is also suggested that the failure of some previous studies on guinea pig cortex in vitro to demonstrate the presence of beta receptors may be due to the particularly rapid desensitization of these receptors.
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PMID:The nature of adrenoceptors in the guinea pig cerebral cortex: a microiontophoretic study. 59 89

1 Rats were convulsed once daily for 7 days by exposure to the inhalant convulsant agent, flurothyl (Indoklon, bis (2,2,2-trifluouroethyl)ether). Twenty four hours after the final convulsion the rats were injected with tranylcypromine (20 mg/kg) followed 30 min later by L-DOPA (50 mg/kg), a procedure which increases brain dopamine concentrations. The flurothyl-treated rats showed a greater locomotor activity response than rats that had not been convulsed.2 This enhanced response appears to be due to increased postsynaptic dopamine receptor sensitivity since flurothyl-treated rats also showed enhanced locomotor responses to methamphetamine (2 mg/kg) and apomorphine (2 mg/kg).3 Enhanced 5-hydroxytryptamine-induced activity responses following administration of tranylcypromine (20 mg/kg) and L-tryptophan (50 mg/kg) were also seen 24 h after the last of 10 daily flurothyl-induced convulsions.4 The increased 5-hydroxytryptamine response also appears to be due to increased postsynaptic sensitivity since the flurothyl-treated rats showed increased hyperactivity following administration of tranylcypromine (20 mg/kg) and the suggested 5-hydroxytryptamine agonist, 5-methoxy N,N-dimethyltryptamine (2 mg/kg).5 No change in the brain concentration of 5-hydroxytryptamine, 5-hydroxyindoleacetic acid, tryptophan, dopamine or noradrenaline was observed 24 h after the last of 10 daily flurothyl-induced convulsions, compared to untreated rats. The rate of 5-hydroxytryptamine accumulation after tranylcypromine/L-tryptophan treatment and of dopamine and noradrenaline accumulation after tranylcypromine/L-DOPA treatment was similar in both groups.6 Repeated flurothyl convulsion has the same effects on these behavioural tests as repeated electroconvulsive shock. Since both treatments have been used successfully to treat depression, it is suggested that the mechanism of action of electroconvulsive therapy may be by increasing postsynaptic responses to the monoamine neurotransmitters.
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PMID:Repeated exposure of rats to the convulsant agent flurothyl enhances 5-hydroxytryptamine- and dopamine-mediated behavioural responses. 63 11


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