Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In generalized, non-convulsive, absence epilepsy, spike-and-wave discharges (SWD) are recorded in both the cortex and the thalamus. The effect of various cortical and thalamic lesions on the occurrence of spontaneous SWD was examined in rats from a strain with genetic absence epilepsy. Cortical ablations suppressed SWD recorded in the thalamus. KCl induced unilateral cortical spreading depression and transiently suppressed SWD in the ipsilateral cortex and thalamus; SWD recovered simultaneously in both structures. Bilateral thalamic lesions of the anterior nuclei, the ventromedial nuclei, the posterior area, or lesion of the midline nuclei did not suppress cortical SWD. However, large lesions of the lateral thalamus, including the specific relay and reticular nuclei, definitely suppressed ipsilateral SWD, and pentylenetetrazol, THIP or gammabutyrolactone failed to restore the cortical SWD. These results demonstrate that the neocortex and the specific thalamic nuclei are both necessarily involved in the generation of SWD in absence epilepsy.
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PMID:Cortical and thalamic lesions in rats with genetic absence epilepsy. 151 95

In order to define the modulatory role played by gamma-aminobutyric acid (GABA) in corticopetal cholinergic projections, the effect of this amino acid and related drugs on gross behaviour, the EEG and the release of acetylcholine (ACh) from the cerebral cortex in freely moving guinea-pigs was studied. gamma Aminobutyric acid, injected intracerebroventricularly (20-50 mumol) induced a three-phase picture: first (5-15 min) behavioural activation and increased release of ACh, then (30-90 min) depression, EEG synchronization and reduced release of ACh, and finally "rebound" stimulation. Ethanolamine-O-sulphate (EOS) injected intraventricularly (28 mumol/kg) or intraperitoneally (14 mmol/kg) reproduced the first two phases of the effects of GABA (i.e. stimulation followed by inhibition), while diazepam (0.7 and 3.5 mumol/kg, i.p.) and flurazepam (32 mumol/kg, i.p.) caused, at first, only depression. Muscimol and 4,5,6,7-tetrahydroisoxazolo(4,5-c)pyridine-3-ol (THIP) injected intraventricularly (in the nmol range) or intraperitoneally (in the mumol range) produced behavioural activation and increased release of ACh; the depressant signs appeared only after very large, toxic doses. Picrotoxin and bicuculline, at sub-convulsive doses, reduced the symptomatology caused by GABA and antagonized the sedation produced by diazepam. Methysergide (8-16 mumol/kg, i.p.) prevented the behavioural activation and the increased release of ACh by GABA, unmasked the depression due to subthreshold doses of diazepam (i.c.v., 7-70 nmol) and reversed the stimulation induced by muscimol into sedation and reduced the outflow of ACh. Pretreatment with 5,7-HT also dampened and shortened the stimulation by muscimol.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The modulation of cortical acetylcholine release by GABA, GABA-like drugs and benzodiazepines in freely moving guinea-pigs. 286 May 90

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 aim of this study was to evaluate the cardiorespiratory effects of intravenously administered gamma-aminobutyric acid (GABA) alpha-(4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol, THIP) and beta-(baclofen) receptor agonists and to locate the site of action of these drugs in the brain. THIP and baclofen were administered to alpha-chloralose-anesthetized cats while minute ventilation (VE), arterial blood pressure (AP), and heart rate were monitored. THIP, in doses of 0.5 to 2 mg/kg decreased VE, tidal volume (VT), and AP. No changes in respiratory rate (f) or inspiratory (TI) or expiratory (TE) duration were observed. Baclofen, in doses of 0.5 to 4 mg/kg, decreased VE, f, and AP. VT and TI increased and an "apneustic" breathing pattern was seen. THIP (9.5 micrograms), applied bilaterally to the glycine-sensitive area of the ventral medulla, reproduced the effects seen with intravenous administration. Application of 10 micrograms of bicuculline bilaterally to this area reversed the effects of intravenous THIP but not those of baclofen. Baclofen (5.6-56 micrograms), administered by the intracisternal route, produced the same respiratory effects seen with intravenous administration. We conclude that activation of GABA alpha- and beta-receptors produces cardiorespiratory depression. However, this is accomplished by different mechanisms and by actions exerted at different central nervous system sites.
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PMID:Respiratory depressant effects of GABA alpha- and beta-receptor agonists in the cat. 303 27

Subcutaneous chronic desipramine (DMI, 5 mg/kg once daily for 18 consecutive days) prevented subcutaneous THIP (20 mg/kg) reduction in body temperature but did not affect THIP behavioral depressant effect (open-field behavior). Repeated DMI treatment did not affect subcutaneous baclofen (2.5-10 mg/kg) reduction in body temperature and behavioral depression (open-field behavior).
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PMID:Functional responses to baclofen and 4,5,6,7-tetrahydroisoxazolo (5,4-c) pyridin-3-ol (THIP) in rats repeatedly treated with desipramine. 335 25

We studied the effect of a gamma-aminobutyric acid (GABA)-A receptor-induced postsynaptic inhibition on regional CBF (rCBF) in awake humans. For this purpose we used a new specific GABA-A agonist, 4,5,6,7-tetrahydroisoxazolo(5,4)-pyridin-3-ol (THIP). As part of a new diagnostic procedure for the determination of which hemisphere subserved language, THIP was infused into the internal carotid artery 20 s before measurement of the rCBF. Administered by this route the THIP is distributed to the neocortex and neostriatum. THIP induced a dosage-dependent decrease of the rCBF. The rCBF decrease was not due to any direct effect on the cerebral vessels. The efficiency of the THIP-induced postsynaptic inhibition was tested by having the subjects voluntarily activate the inhibited cortex. During submaximal inhibition the subjects were able voluntarily to counteract decreases of rCBF in superior frontal cortex and motor cortex. Larger doses of THIP abolished this response and depressed the rCBF to baseline levels (20 ml/100 g/min). This was associated with 10-min total depression of function of the anterior two-thirds of the injected hemisphere. An analysis of the changes of rCBF in activated and nonactivated cortex--with and without THIP-induced inhibition--showed that it would be very unlikely that average increases in synaptic inhibition would increase rCBF in neocortical areas. Intracarotid injection of the water-soluble, nonirritative THIP is a very useful alternative to sodium amytal injection for determination of hemispheric dominance.
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PMID:The effect of the GABA-A agonist THIP on regional cortical blood flow in humans. A new test of hemispheric dominance. 336 94

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

The effects of withdrawal from long-term treatment with increasing concentrations of sodium barbital in the drinking water were studied in rats. Animals were tested 72 hr after the removal of the drug. Withdrawal of barbital induced a significant leftward displacement of the dose-response curves obtained for the convulsive effects of strychnine, picrotoxin and 3-mercaptopropionic acid. The removal of the drug also made the rats more sensitive to convulsions elicited by sound. Baclofen and THIP were able to decrease the audiogenic response score of rats, withdrawn from barbital, in a dose-dependent way. These effects were interpreted to be a consequence of changes in the sensitivity of central GABAA and/or noradrenergic receptors induced by depression due to long-term administration of barbital.
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PMID:Central nervous system supersensitivity and withdrawal from long-term treatment with barbital. 409 60

THIP, 4, 5, 6, 7-tetrahydroisoxazolo (5,4-) pyridin-3-ol, is a GABA-agonistic drug with analgesic effect, but apparently without respiratory depressant properties in awake subjects. The effect of THIP on the CO2 ventilation response was tested before, during and at the end of halothane anaesthesia in six male patients and compared to a control group. As there was no indication of respiratory depression by THIP, the drug may have a future in the treatment of postoperative pain if an analgesic effect is confirmed under clinical conditions.
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PMID:Respiratory effect of THIP, a GABA-agonistic analgesic, during halothane anaesthesia. 635 58

The sensitivity of Purkinje cells (PCs) and neurons of the cerebellar nuclei (NCNs) to iontophoretic application of gamma-aminobutyric acid (GABA), 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol (THIP) and baclofen, i.e., GABAA and GABAB agonists respectively, have been studied in anesthetized rats. All the agonists produced dose-dependent firing rate depression of the PCs but with different potencies. The inhibitory actions of both GABA and THIP were specifically antagonized by bicuculline (Bic) and the baclofen-induced responses by 2-hydroxysaclofen. GABA and THIP also depressed the spontaneous activity of NCNs while baclofen was ineffective. The present results therefore suggest that GABAA receptors are involved in the GABA-induced inhibition in the cerebellar cortex and in the cerebellar nuclei and GABAB receptors are involved only in the cerebellar cortex.
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PMID:GABA, THIP and baclofen inhibition of Purkinje cells and cerebellar nuclei neurons. 838 66


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