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)

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

Neonatal seizures can result in long-term adverse consequences including alteration of seizure susceptibility and impairment in spatial memory. However, little is known about the effects of neonatal seizures on developmental changes occurring in synaptic transmission during the first postnatal weeks. The purpose of the present study was to examine the effect of neonatal seizures on several aspects of gamma-aminobutyric acid (GABA)ergic and glutamatergic synaptic transmission in the developing rat hippocampus. Flurothyl was used to induce multiple recurrent seizures in rat pups during the first postnatal days. Whole-cell patch-clamp recordings from the hippocampal CA3 pyramidal cell and extracellular recordings from the CA3 pyramidal cell layer were made in slice preparations. In rats that experienced neonatal seizures the amplitude of spontaneous inhibitory postsynaptic currents at P15-17 was decreased by 27% compared with controls, whereas neither frequency nor the kinetic properties were altered. Neonatal seizures did not affect the timing of the developmental switch in the GABAA signaling from excitatory to inhibitory. None of the studied parameters of glutamatergic postsynaptic currents was different between the flurothyl and control groups, including the amplitude and frequency of the spontaneous excitatory postsynaptic currents, the ratio of the amplitudes and frequencies of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA)-mediated spontaneous postsynaptic currents, and the kinetics of AMPA and NMDA mediated postsynaptic currents in the age groups P8-10 and P15-17. We suggest that the selective depression of the amplitude of GABAergic synaptic responses may contribute to the adverse neurological and behavioral consequences that occur following neonatal seizures.
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PMID:Selective impairment of GABAergic synaptic transmission in the flurothyl model of neonatal seizures. 1655 19