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

The action of different classes of clinically effective antidepressants and electroshock on gamma-aminobutyric acid (GABA) B recognition sites in the frontal cortex was compared to that of other psychotropic agents. After either prolonged (6-18 days) s.c. infusion via osmotic minipumps or repeated i.p. injections of different antidepressants, or a series of electroshocks, treatment was halted and 72 hr later the animals were sacrificed, the brain was dissected and frozen. All major antidepressants (desipramine, amitryptyline or maprotiline), several newer compounds with reported antidepressant activity (viloxazine, zimelidine, fluoxetine, citalopram, progabide, fengabine, sodium valproate, mianserin, trazodone or nomifensine) as well as pargyline and repeated electroshocks, up-regulated GABA B binding in the rat frontal cortex but not hippocampus. This appeared to be a maximum binding effect, but in some instance the kinetics were more complex. Reserpine, diphenylhydantoin and phenobarbital down-regulated GABA B binding in the frontal cortex, whereas this was unaltered by haloperidol, chlorpromazine or diazepam administration. Desipramine up-regulated GABA B binding in a dose- and time-dependent manner (minimum effective dose, 1.25 mg/kg/day s.c. for 18 days; onset of action, 6 days at 5 mg/kg/day s.c.). Together with the rather sparse data in the literature on GABA in depression and antidepressant drug action, these findings support a common GABAergic mechanism of action of antidepressant drugs and electroshock, mediated via GABA B synapses.
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PMID:Upregulation of gamma-aminobutyric acid (GABA) B binding sites in rat frontal cortex: a common action of repeated administration of different classes of antidepressants and electroshock. 299 46

Reserpine-induced depression has been used as an animal model to screen for antidepressant agents. Chronic (14-day) treatment with reserpine resulted in a significant increase in beta-adrenergic receptor binding in the cerebral cortex and the hippocampus, which was partially prevented by chronic treatment with either the antidepressant imipramine, the GABA-A agonist THIP or, the GABA-B agonist baclofen. Chronic treatment with reserpine also significantly increased 3H-GABA receptor binding, which was partially prevented by chronic treatment with either imipramine or THIP. Both subchronic and chronic administration of reserpine resulted in a decrease in GABA concentrations in the cerebral cortex and hippocampus. These data demonstrate the effect of reserpine treatment on the GABA-ergic system, and add further support for a functional coupling between the noradrenergic and GABA-ergic systems, which may be important for the mechanism of action of antidepressant agents.
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PMID:GABAergic effects of reserpine following chronic treatment. 299 46

The effect was studied of tranquilizer reserpine on the performance of Hubbard chicks. The results can be summed up as follows: The supplementation with reserpine at levels of 0.25 and 0.5 ppm decreased the final body weight, and the growth depression was more pronounced at the higher doses. Supplementation by 0.25 ppm reserpine improved the feed efficiency as compared with the control group, whereas this efficiency deteriorated on supplementation with 0.5 ppm. The mortality rates were 13.5% for the control group and 0.0 and 2.7% for the groups with 0.25 and 0.5 ppm of reserpine, respectively. Reserpine supplementation had no significant effect on the percentage of the dressing carcass, edible giblets, feathers, head and feet.
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PMID:Effect of reserpine on the performance of broiler chicks. 361 74

The cardiovascular (blood pressure, heart rate, cardiac contractility) effects of i.v. gamma-aminobutyric acid (GABA) were investigated in guinea-pigs anaesthetized with barbitone or urethane. GABA (0.1-10 mg kg-1) produced a transient 'depressive' effect on cardiovascular parameters which in barbitone-anaesthetized animals was followed by a transient 'excitatory' effect. Resting cardiovascular parameters were higher in urethane-as compared to barbitone-anaesthetized animals. Picrotoxin pretreatment (2 mg kg-1, i.v.) barely affected the cardiovascular changes produced by GABA in barbitone-anaesthetized animals. In picrotoxin pretreated animals anaesthetized with urethane, GABA produced an initial depression of cardiovascular parameters followed by an excitatory phase. Hexamethonium (20 mg kg-1, i.v.) suppressed or reduced markedly the GABA-induced cardiovascular changes both in barbitone- or urethane- anaesthetized animals. Reserpine pretreatment lowered resting cardiovascular parameters. In these animals, regardless of type of anaesthesia, the effects of i.v. GABA were of the 'excitatory' type only. Reserpine pretreated animals anaesthetized with barbitone were selected for further experiments. Various GABAA receptor agonists (homotaurine, muscimol, THIP, 5-aminovaleric acid) mimicked the 'excitatory' effect of GABA in reserpine pretreated animals anesthetized with barbitone and prevented the effects of subsequent GABA administration. On the other hand (+/-)-baclofen, a selective GABAB receptor agonist, had a slight depressant effect and did not prevent the 'excitatory' cardiovascular effects of GABA. Neither bicuculline nor picrotoxin pretreatment prevented the 'excitatory' cardiovascular effect of i.v. GABA in reserpine pretreated, guinea-pigs anaesthetized with barbitone. In adrenalectomized guinea-pigs or in preparations receiving i.v. phentolamine plus propranolol, GABA produced only a small 'depressant' effect on cardiovascular parameters. These findings demonstrate that GABA exerts a neuromodulatory effect on cardiovascular function via peripheral actions which is influenced by: type of anaesthesia resting values of cardiovascular parameters degree of activity of the sympathetic nervous system and catecholamine release from the adrenal medulla.
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PMID:Differences in cardiovascular responses to peripherally administered GABA as influenced by basal conditions and type of anaesthesia. 374 54

1. In the unanaesthetized cat, an injection of 0.75 mg of morphine into a lateral cerebral ventricle produced strong hyperglycaemia; on intravenous injection, 10 to 30 times larger doses were required. Other effects produced with both injections were shivering, pupillary dilatation, opening of the eyes, miaowing, periods of excitation, and analgesia. Between the periods of excitation the cat did not react to objects moving in front of its eyes and it had a vacant stare.2. Noradrenaline, adrenaline, and 5-hydroxytryptamine (5-HT) injected intraventricularly (250 mug, twice) depressed the hyperglycaemia due to intraventricular morphine, and noradrenaline also depressed the hyperglycaemia due to intravenous morphine. Adrenaline produced the strongest and 5-HT the weakest depression. 5-HT did not depress the other effects of morphine, but the catecholamines depressed most of them; only analgesia and the vacant stare appeared to be unaffected.3. Reserpine injected intraventricularly (0.5 mg, twice) greatly accentuated the hyperglycaemia as well as the other effects produced by intraventricular morphine, but pupillary dilatation and opening of the eyes no longer occurred; the protrusion of the nictitating membranes produced by the reserpine persisted.4. Pentobarbitone sodium injected intraperitoneally in an anaesthetizing dose practically abolished the morphine hyperglycaemia, but injected intraventricularly in a dose of a few milligrammes, it had a two fold effect: depression followed by enhancement of the morphine hyperglycaemia. The enhancement may be due to sensitization of the effect of the adrenaline released by morphine, since adrenaline hyperglycaemia was enhanced as well.5. Morphine did not seem to act on structures in the walls of either the lateral or third ventricle when producing its hyperglycaemic effect on intraventricular injection. The action may therefore be on more caudally situated parts of the neuro-axis, on the central grey, on structures in the floor of the fourth ventricle or of the lateral recesses, or even on structures near the ventral surface of the brain stem.
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PMID:The hyperglycaemic effect of morphine. 465 65

1. Infusion of daunomycin 50 mg/kg in the monkey consistently induced ventricular arrhythmias which were not influenced by bilateral vagotomy.2. A central sympathetic component to the arrhythmias was suggested because spinal transection, ganglionic blockade or bilateral stellate ganglionectomy prevented any alterations in the e.c.g.3. Bilateral adrenalectomy or splanchnic nerve section protected three of six animals. This source of catecholamines may not be necessary in every case to initiate the arrhythmia.4. Guanethidine was a relatively ineffective antiarrhythmic agent. Timing appears to be important with this agent.5. Pargyline, by monoamine oxidase inhibition or other mechanisms, significantly lowered the arrhythmic dose of daunomycin. Reserpine pretreatment, on the other hand, prevented any e.c.g. alterations following daunomycin.6. Phenoxybenzamine exerted significant protection which may be related to its cardiodepressant properties.7. Alterations in e.c.g. were seen in all (+)-propranolol pretreated animals, although the arrhythmic period was modified in two of three experiments. Racemic (+/-) propranolol, which exerts direct myocardium depression as well as beta-adrenoceptor blockade, was completely protective in four of five experiments. The results of the present experiments indicate that the sympathetic nervous system is intimately involved in the daunomycin arrhythmia.
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PMID:Role of the sympathetic nervous system in daunomycin-induced arrhythmia in the monkey. 499 May 92

Reserpine was administered daily by intubation for 81 days to 3 rhesus monkeys to investigate a possible relationship with depression. Their behavior during the experimental period was compared to their behavior before and after the drug period, as well as to that of a control group of 3 monkeys given water instead of reserpine. Experimental findings were as follows: 1) Reserpine caused significant behavioral changes in the rhesus monkey. These changes included decreases in visual exploration and locomotion, and increases in self-huddling, posturing, and tremor; and 2) the behavioral effects of repeated daily dosage were not cumulative nor was tolerance developed by the drugged monkeys. There was no visible effect 15 hours after each daily drug administration. The behavioral alterations were not detectable more than 15 hours following each daily dose. It was noted that the data were insufficient to justify the conclusion that reserpine administration produced depression in the monkey subjects, even though it did have marked behavioral effects on them.
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PMID:Effects of reserpine on the social behavior of rhesus monkeys. 500 59

The time course of the nicotinic acid-induced changes in levels of plasma free fatty acids (FFA) was examined. The plasma FFA response of fasted dogs to graded doses of nicotinic acid was shown to be biphasic: an initial depression of the level of plasma FFA was followed by a rebound elevation to supernormal levels. FFA rebound was not seen after the administration of the nicotinic acid homologue, pyridylacetic acid, or a variety of nicotinic acid metabolities. A similar pattern of FFA response was observed in fasted, normal rats. Adrenalectomy did not abolish the secondary elevation of FFA but did cause a somewhat delayed response. Hypophysectomy modified the time course of the response-the initial FFA decrease was prolonged-and the intensity of the FFA rebound was diminished. No rebound was observed in hypophysectomized, adrenalectomized rats. In normal rats, nicotinic acid caused a significant rise in the level of plasma corticosterone. A normal rebound pattern was observed in thyroidectomized rats. Reserpine, administered on a schedule designed to deplete catecholamine stores, altered the time course of plasma FFA changes only slightly. The results indicate that both the pituitary and adrenal functions are required for the expression of the rebound phenomenon after nicotinic acid administration.
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PMID:The plasma free fatty acid rebound induced by nicotinic acid. 603 64

An operant conditioning apparatus for studies in equine pharmacology was constructed. Horses interacted with this apparatus by breaking a light beam and were rewarded with 30 ml of oats. Horses readily learned to use this apparatus and were trained to respond on a variable-interval-60 schedule. With this schedule, there was no direct relationship between the rate of light beam breaking and the reward. Horses thus developed their own individual response rates (ie, light-beam breaking rates), and these rates remained stable at between 5 and 35 responses/min for each horse over a period of months. The effects of 2 drugs on this paradigm were tested. Reserpine (5 mg/horse, IV) depressed the response rate in all horses tested. This depression was maximal between 3 and 5 days after treatment and lasted for up to 10 days. After small doses of cocaine (0.01 mg/kg of body weight IV), the response rate of 1 horse was stimulated, whereas 1 mg of cocaine/kg was required for maximal stimulation of response rate in another horse. Larger doses of cocaine inhibited response. Variable-interval response was a sensitive method of measuring drug effects in the horse and allowed accurate quantitation of drug effects that were not detectable by clinical observation.
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PMID:Variable-interval responding in the horse: a sensitive method of quantitating effects of centrally acting drugs. 710 92

Reserpine caused a decrease in the state 3, respiratory control ratio (RCR) and ADP/O ratio in frontal cortex, striatum and liver of rats 1 h after drug administration. State 4 respiratory rate was stimulated in frontal cortex and striatum. In the liver, 6-OHDA decreased the ADP/O ratio when both pyruvate/malate and succinate were used as substrates. Reserpine induced changes in the activities of Na+K(+)-ATPase and Mg(2+)-ATPase in frontal cortex and liver 15 min and 4 h after administration of the drug. In the liver only 6-OHDA caused the depression of Mg(2+)-ATPase activity (P < 0.05). Reserpine altered the levels of K+, Na+ and Ca2+ cations in rat frontal cortex and striatum, while 6-OHDA caused a decrease in the amount of Mg2+ in liver (P < 0.05).
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PMID:Inhibition of rat mitochondrial functions in vivo by 6-OHDA and reserpine. 805 58


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