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

The effects of diazepam, flunitrazepam, phenobarbitone and baclofen on excitatory as well as on pre- and postsynaptic inhibitory processes in the cuneate nucleus were studied in decerebrate cats. Afferent presynaptic inhibition in the cuneate nucleus, evoked by volleys in the median nerve, and assessed by the size of the positive cuneate surface potential (P wave), the dorsal column reflex (DCR), and the increased excitability of primary afferent terminals of the ulnar nerve, was markedly enhanced by diazepam (0.1-3.0 mg/kh i.v.) and flunitrazepam (0.01-0.3 mg/kg i.v.), slightly enhanced by lower doses of phenobarbitone (3-20 mg/kg i.v.), but depressed by baclofen (1-10 mg/kg i.v.). Diazepam, flunitrazepam and phenobarbitone also increased postsynaptic inhibition in the cuneate nucleus which was measured by the decrease after conditioning volleys in the median nerve of the short-latency lemniscal response to cuneate stimulation. The GABA receptor blocking agent, picrotoxin, antagonized the effects of diazepam on pre- and postsynaptic inhibition in a surmountable way. After thiosemicarbazide (TSC), an inhibitor of GABA synthesis, both pre- and postsynaptic inhibition were greatly reduced and the augmenting effect of diazepam on both types of inhibition was nearly abolished. Aminooxyacetic acid (AOAA), an inhibitor of GABA degradation, slightly enhanced pre- and postsynaptic inhibition; the effects of diazepam were unaffected by AOAA. Diazepam, flunitrazepam and phenobarbitone did not alter the resting excitability of primary afferent endings or of cuneo-thalamic relay (CTR) cells in the cuneate nucleus. After higher doses (30 mg/kg i.v.) of phenobarbitone pre- and postsynaptic inhibition, which were enhanced by 10 mg/kg of this drug, tended to return to pre-drug values or below. Phenobarbitone, in contrast to benzodiazepines, also depressed in a dose-dependent way the N wave, which is an index of the orthodromic excitation of the CTR cells. Baclofen strongly depressed the cuneate N wave, decreased the excitability of CTR cells, reduced pre- and postsynaptic inhibition, but had no effect on the resting excitability of primary afferent endings. Our findings suggest the following modes of action of the above mentioned drugs: 1. benzodiazepines enhance selectively the GABA-mediated pre- and postsynaptic inhibition in the cuneate nucleus; 2. phenobarbitone slightly enhances pre- and postsynaptic inhibition only in a narrow dose range, and in addition reduces the excitatory processes in the cuneate nucleus; 3. baclofen seems to depress the excitation of cuneate relay cells and interneurones postsynaptically; the depression of relay cells is probably nonspecific.
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PMID:Effects of two benzodiazepines, phenobarbitone, and baclofen on synaptic transmission in the cat cuneate nucleus. 1 11

Intravenous baclofen (1 mg/kg) abolished or severely attenuated the high threshold late component (but not the low threshold early component of long duration (greater than 150 msec) discharges evoked in cat dorsal horn neurons by intense transcutaneous electrical stimulation. Baclofen similarly reduced the spontaneous activities and discharges evoked by intra-arterial bradykinin in these same cells. These powerful inhibitions of dorsal horn interneurons may be the basis of baclofen's reported analgesic actions and could contribute to depression in reflex excitability of motoneurons.
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PMID:Effects of intravenous baclofen on dorsal horn neurons of spinal cats. 21

Effects of beta-(p-chlorophenyl)-GABA (baclofen), a muscle relaxant, on the response of mice and rats to various noxious stimuli were studied. In mice, 5 approximately 10 mg/kg i.p. of baclofen delayed the response time to tail-pinch and hot-plate stimuli but the relaxation was also apparent with this dose range. Mephenesin also delayed the response time to tail-pinch stimuli with the dose producing muscle relaxation. Baclofen, 3 mg/kg i.p., while producing no muscle relaxation, suppressed the acetic acid-induced writhing. The same effect, suppression of writhing and no muscle relaxation, was achieved with 50 mg/kg i.p. of mephenesin. In rats, baclofen (5 approximately 10 mg/kg i.p.) increased the response threshold in Randall-Selitto method and suppressed the bradykinin-induced symptoms, however, muscle relaxation was also produced with these same doses. Increase in response threshold in Randall-Selitto method was achieved with the dose of mephenesin producing muscle relaxation. The time courses of the depression of response to noxious stimuli and the muscle relaxation induced by baclofen and mephenesin were consistent in mice and rats. A small dose (3 mg/kg i.p. in mice, 2 mg/kg/h s.c. in rats) of baclofen reduced the antinociceptive effect of morphine but a larger dose (5 mg/kg i.p. in mice, 7 mg/kg/h s.c. in rats) of baclofen increased or did not alter the effect of morphine. It seems likely that the antinociceptive effect of baclofen may be nonspecific to analgesia.
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PMID:[Effects of beta-(p-chlorophenyl)-GABA (baclofen) on response to noxious stimuli (author's transl)]. 59 82

A double-blind cross-over trial of the effects of baclofen and placebo was carried out in 20 female patients suffering from neuroleptic-induced tardive dyskinesia. After 14 days of treatment 15 patients showed improvement of baclofen, whereas none showed improvement on placebo; baclofen was thus significantly more effective than placebo. Baclofen is a GABA-like drug which passes through the blood-brain barrier and which reduces the neuroleptic-induced increase of dopamine turn-over. In tardive dyskinesia is found dopaminergic hypersensitivity, and baclofen is supposed to exert its action by inhibiting the dopamine activity. Side effects, although temporary, were observed in the form of sedation, muscular hypotonia, dizziness, vomiting, and muscular rigidity. One patient developed a depression. Baclofen or other gabergic drugs used in the treatment of dyskinesias do not increase the dopaminergic hypersensitivity, which is part of the pathogenesis of these conditions; gabergic therapy must therefore be preferred to treatment with dopamine receptor blocking drugs.
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PMID:Baclofen (Lioresal) in the treatment ofneuroleptic-induced tardive dyskinesia. 78 59

Somatostatin and gamma-aminobutyric acid (GABA) are co-localized in some neurons in the CA1 area of the hippocampus. Since it is possible that the peptide and the amino acid are co-released, the interactions between the actions of somatostatin and GABA-ergic inhibitory post-synaptic potentials (IPSPs) in the CA1 pyramidal neurons of guinea pig hippocampal slices have been investigated. Somatostatin (2 microM) induced a hyperpolarization of the CA1 neurons associated with a reduction in the input resistance of the cells. These effects were not blocked by picrotoxinin (20 microM) or phaclofen (1 mM). Chelation of intracellular Ca2+ (Ca2+i) with BAPTA or the inhibition of protein kinase C (PKC) with sphingosine (30 microM) had no significant effects on the hyperpolarizing actions of somatostatin. The peptide suppressed the GABAA receptor-mediated fast IPSPs and the GABAB receptor-mediated slow IPSPs, but had no significant effect on the excitatory post-synaptic potentials (EPSPs). Somatostatin-induced depression of the IPSPs was not due to the hyperpolarization of the neurons. Baclofen (20 microM) suppressed the EPSP, as well as the fast and the slow IPSPs. The hyperpolarization of the CA1 neurons caused by somatostatin was greatly reduced in the presence of baclofen, an effect that was not due to the hyperpolarization of the cell by baclofen. The presence of QX-314 in the CA1 neurons, which suppressed the Na+ spikes and the slow IPSPs, prevented the hyperpolarization of the neurons by somatostatin and baclofen.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Actions of somatostatin on GABA-ergic synaptic transmission in the CA1 area of the hippocampus. 135 22

Four cases of baclofen intoxication are reported, with a review of 33 cases from the literature. Analysis of these 37 cases suggests that there are two types of baclofen intoxication syndrome. Patients with acute intoxication present with four major clinical manifestations: encephalopathy (disturbance of consciousness and/or seizure), respiratory depression, muscular hypotonia, and generalized hyporeflexia. Patients with chronic intoxication present with hallucinosis, impaired memory, catatonia, or acute mania. The acute intoxication syndrome has a faster onset, shorter duration, more severe clinical manifestations, and higher incidence of seizures than the chronic intoxication syndrome. Baclofen intoxication, although it may cause grave encephalopathic manifestations and electroencephalographic findings, has a benign outcome if actively managed.
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PMID:Baclofen intoxication: report of four cases and review of the literature. 157 99

1. We examined the effects of gamma-aminobutyric acid (GABA) and baclofen on pre- and postsynaptic membrane conductances in dissociated rat hippocampal cells. Both GABA (5 microM with 10 microM-bicuculline) and baclofen (50 microM) caused small but significant increases in membrane conductance that were blocked by 2-hydroxysaclofen (100 microM), a GABAB receptor antagonist. This increase in membrane conductance seems to be mediated by GABAB receptors. 2. At a low concentration of GABA (1 microM) which has a very small direct postsynaptic effect on GABAA receptors, no postsynaptic GABAB effect was detected. However, at this concentration, GABA near maximally attenuated both excitatory and inhibitory synaptic currents. This GABA effect on transmitter release was significantly attenuated by 2-hydroxysaclofen. 3. Baclofen was also more potent in attenuating the inhibitory synaptic conductance than increasing postsynaptic conductance. Concentrations below 1 microM diminished synaptic currents by greater than 50%. At these low baclofen concentrations 2-hydroxysaclofen significantly attenuated baclofen's reduction of synaptic currents. 4. The effects of GABA and baclofen on synaptic conductances were blocked by pretreating the cultures with pertussis toxin, suggesting that a GTP-associated protein, Gi or Go is responsible for reducing transmitter release. 5. Despite the ability of GABA to diminish inhibitory synaptic currents through GABAB receptor activation, we observed no effect of 2-hydroxysaclofen on paired-pulse depression. Therefore, these presynaptic GABAB receptors may not be true 'autoreceptors'. 6. Our findings indicate that in culture, at least, the presynaptic GABAB effect responsible for synaptic modulation has a pharmacological profile similar to the postsynaptic GABAB effect. At present, it is unnecessary to postulate two different types of GABAB receptors.
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PMID:The modulation of rat hippocampal synaptic conductances by baclofen and gamma-aminobutyric acid. 166 62

The mechanism of disinhibition produced by (+/-)-baclofen was studied using intracellular recording in area CA1 of rat hippocampal slices. Baclofen reversibly depressed monosynaptic IPSPs evoked by direct activation of interneurons in the presence of the excitatory amino acid receptor antagonists 6,7-dinitroquinoxaline-2,3-dione (DNQX) and D,L-2-amino-5-phosphonovalerate (APV). Ba2+ prevented baclofen-induced hyperpolarization of pyramidal neurons but not depression of monosynaptic IPSPs by baclofen. Baclofen reversibly depressed monosynaptic IPSPs when applied close to the recording site, but was ineffective when applied close to the stimulating site in stratum radiatum. These results suggest that baclofen disinhibits pyramidal neurons in area CA1 of the rat hippocampus by activating receptors on the terminals of inhibitory neurons that are coupled to a Ba(2+)-insensitive effector mechanism.
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PMID:Baclofen-induced disinhibition in area CA1 of rat hippocampus is resistant to extracellular Ba2+. 167 68

GABAB mechanisms have been implicated in the antinociceptive, but not anticonvulsant effects of carbamazepine. A variety of antidepressants have been reported to upregulate GABAB receptors after chronic administration. The GABAB agonist l-baclofen was studied in depressed patients based on two separate rationales. l-Baclofen, in doses ranging from 10-55 mg/day, was administered to five patients with primary affective disorder. No patient showed a positive clinical response, while three patients showed a pattern of increasing depression or cycling during treatment and improvement during withdrawal. These preliminary data suggest that GABAB agonism is unlikely to produce antidepressant effects and may be unrelated to the mechanism of carbamazepine's antidepressant action. These data, taken with a reinterpretation of other findings that antidepressant modalities upregulate GABAB receptors in brain following chronic administration, suggest that GABAB antagonism rather than agonism may be a fruitful clinical strategy to explore in depression.
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PMID:Lack of beneficial effects of l-baclofen in affective disorder. 181 78

1. Intracellular recordings were made from antidromically identified motoneurones in transverse spinal cord slices from neonatal (12-16 day) rats. 2. Superfusion of (+/-)-baclofen (0.5-50 microM) reduced the excitatory postsynaptic potentials (e.p.s.ps) and inhibitory postsynaptic potentials (i.p.s.ps) evoked by dorsal root or dorsal root entry zone stimulation in a concentration-dependent manner; the calculated EC50 was 2.4 microM. Baclofen in comparable concentrations also reversibly eliminated spontaneously occurring e.p.s.ps and i.p.s.ps. 3. (-)-Baclofen was more effective as compared to baclofen in reducing the synaptic responses, whereas (+)-baclofen at concentrations as high as 50 microM was ineffective. 4. Baclofen (less than 5 microM) attenuated the synaptic responses without causing a significant change of passive membrane properties and depolarizations induced by exogenously applied glutamate. In addition to synaptic depression, baclofen (greater than 5 microM) caused a hyperpolarization associated with decreased membrane resistance in some of the motoneurones; the glutamate responses were also attenuated. 5. Baclofen reversibly depressed the spike after-hyperpolarization of the motoneurones. 6. GABA (1-10 mM) depressed synaptic transmission and depolarized or hyperpolarized motoneurones. While potentiated by the uptake inhibitor nipecotic acid, the synaptic depressant effect of GABA was not antagonized by bicuculline. 7. The synaptic depressant effect of baclofen was neither blocked by GABAA antagonists bicuculline and picrotoxin (10-50 microM) nor by the GABAB antagonist phaclofen (0.1-1 mM). 8. It is suggested that baclofen depresses excitatory and inhibitory transmission in rat motoneurones by primarily a presynaptic mechanism in reducing the liberation of chemical transmitters from nerve endings via a phaclofen-insensitive GABAB receptor.
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PMID:Phaclofen-insensitive presynaptic inhibitory action of (+/-)-baclofen in neonatal rat motoneurones in vitro. 215 78


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