The effects of benzodiazepine agonists, inverse agonists and Ro 15–1788 on the responses of the superior cervical ganglion to GABA <i>in vitro</i>

Little, H.J.

doi:10.1111/j.1476-5381.1984.tb10119.x

Cited by 30 publications

(8 citation statements)

References 29 publications

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“…These have previously been demonstrated by in vitro binding (Braestrup & Nielsen, 1981;Mohler, 1982), in vitro electrophysiological (Nutt etal., 1982a;Polc etal., 1982;Little, 1984) and acute behavioural studies (Cowen et al, 1981;File et al, 1982;Nutt et al, 1982b). We have now shown that chronic contragonist treatment also produces opposite changes to those seen during chronic benzodiazepine treatment since kindling may be considered the reverse of tolerance.…”

Section: Chronic Treatmentmentioning

confidence: 99%

Acute and chronic effects of the benzodiazepine receptor ligand FG 7142: proconvulsant properties and kindling

Little

Nutt

Taylor

1984

British J Pharmacology

133

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The effects of the acute and chronic administration of the ,B-carboline benzodiazepine receptor ligand, FG 7142 were studied in mice. 2 On acute administration FG7142 (at doses between 10 and 40mgkg-1) lowered seizure thresholds to infused pentylenetetrazol (PITZ) but showed an unusual dose-response curve in that higher doses had less effect. The duration of action was considerably longer than that of other 1-carbolines, such as ethyl-1-carboline-3-carboxylate (ICCE). 3 During repeated administration, doses of FG 7142 which were initially proconvulsant subsequently produced generalized seizures on average in 60% of animals after 12 once daily treatments. This seemed to be a form of chemical kindling. 4 The effects of different drug administration regimes were studied. Once daily dosage was shown to be the optimum for kindling production, and was therefore used for subsequent experiments. 5 Kindling lasted for at least one month after 12 single once daily doses of 40mg kg-(FG 7142). 6 The administration of the benzodiazepine antagonist Ro 15-1788 concurrent with FG 7142 prevented kindling. When Ro 15-1788 was given to kindled animals along with a challenge dose of FG 7142, it prevented the expression of kindled seizures. These data show that kindling is mediated via the benzodiazepine receptor.

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Section: Chronic Treatmentmentioning

confidence: 99%

Acute and chronic effects of the benzodiazepine receptor ligand FG 7142: proconvulsant properties and kindling

Little

Nutt

Taylor

1984

British J Pharmacology

133

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“…In each case we used two or more methods in order to determine the activity of a drug. The chronic treatment with FG 7142 (see below) was kept constant, using a 12 day schedule which we have shown previously to be optimal in this strain ofmice (Little et al, 1984). In all cases the 'challenge' tests on the acute actions of the drugs under study were carried out one week after the end of the twelve day treatment (day 19), a time at which we know the kindling phenomenon is still present.…”

Section: Methodsmentioning

confidence: 99%

“…The latter group include P-carboline compounds such as P-CCE (ethyl-p-carboline-3-carboxylate) and FG 7142 (N-methyl-p-carboline-3-carboxamide) and the effects of these, as well as those of benzodiazepines, are blocked by the antagonist Ro (Hunkeler et al, 1981;Nutt et al, 1982). These effects of these three types of compound are reflected in their effects on the actions on the inhibitory transmitter GABA (Little, 1984), and this is thought to be the basis of their in vivo actions.…”

Section: Introductionmentioning

confidence: 99%

The effects of drugs acting at the GABA_A‐receptor/ionophore after chemical kindling with the benzodiazepine receptor ligand FG 7142

Little

Nutt

Taylor

1986

British J Pharmacology

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1 Repeated administration of the P-carboline benzodiazepine receptor ligand FG 7142 produces sensitization to its effects so that full seizures develop (chemical kindling); initially it is only proconvulsant. The present study investigated alterations in the function of drugs which act at the different sites at the y-aminobutyric acid (GABA) benzodiazepine receptor complex, after repeated administration of FG 7142. 2 In FG 7142 kindled mice decreased anticonvulsant and hypothermic effects of the GABA agonist muscimol were observed. The hypothermic effects of the GABA agonist progabide were reduced. In contrast a small increase in the hypothermic effect of pentobarbitone was seen. 3 The convulsant effects of bicuculline and picrotoxin were unaltered when they were given intravenously but marginally increased when they were given by the intraperitoneal route. No changes were seen in the hypothermic effects of these drugs. 4 No significant changes were seen in the convulsant or hypothermic effects of pentylenetetrazol. 5 These results suggest that kindling with FG 7142 may alter GABA receptor function.

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“…GABA-synthesizing and GABA-metabolizing enzymes (glutamate decarboxylase, GAD, and GABA transaminase, GABA-T, respectively) are detectable in SCG by using biochemical (Kanazawa et al, 1976) and immunohistochemical techniques (Hfipp61fi et al, 1987). Both GABA-A and GABA-B binding sites have been identified in SCG (Bowery et al, 1979 c;Balcar etal., 1986), as well as significant effects of GABA in vivo and in vitro (Little, 1984;Farkas etal., 1986;Parducz etal., 1990).…”

Section: Introductionmentioning

confidence: 99%

Neurochemical evidence for a neuronal GABAergic system in the rat sympathetic superior cervical ganglion

Burgos

Rosenstein

Cardinali

1992

J. Neural Transmission

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Some characteristics of gamma aminobutyric acid (GABA) uptake and release in rat superior cervical ganglion (SCG) were investigated. Kinetic analysis of GABA uptake indicated the existence of both high affinity (Km = 18.6 microM) and low affinity (Km = 485 microM) uptake systems. 3H-GABA influx was decreased by inhibitors of glial (beta-alanine), neuronal (2,4-diaminobutyric acid, DABA), or glial and neuronal GABA uptake (nipecotic acid). 3H-GABA efflux was elicited by K+ depolarization in a dose-dependent manner, an effect unaltered by severing the preganglionic nerve fibers. Superfusion of SCG explants with DABA or beta-alanine resulted in increased 3H-GABA efflux from tissue, an effect amplified by the absence of calcium in the superfusion medium. 3H-GABA loading in the presence of DABA, but not in the presence of beta-alanine, resulted in abolition of K(+)-elicited 3H release. At 20 mM, but not at 50 mM K+, the release of 3H-GABA was inhibited by replacing Ca2+ by Mg2+ and by adding EGTA, or by incubating SCG in the presence of the Ca(2+)-channel blocker verapamil. Veratrine evoked GABA release in Ca(2+)-independent manner. None of several putative SCG autacoids or agonists (nicotine, muscarine, norepinephrine, dopamine, serotonin, baclofen, muscimol) significantly modified GABA release.

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The effects of benzodiazepine agonists, inverse agonists and Ro 15–1788 on the responses of the superior cervical ganglion to GABA in vitro

Abstract: 1 The effects of benzodiazepines and their antagonists on the responses to y-aminobutyric acid (GABA) of the superior cervical ganglion of the rat were examined using extracellular recording.

Cited by 30 publications

References 29 publications

Acute and chronic effects of the benzodiazepine receptor ligand FG 7142: proconvulsant properties and kindling

Acute and chronic effects of the benzodiazepine receptor ligand FG 7142: proconvulsant properties and kindling

The effects of drugs acting at the GABA_A‐receptor/ionophore after chemical kindling with the benzodiazepine receptor ligand FG 7142

Neurochemical evidence for a neuronal GABAergic system in the rat sympathetic superior cervical ganglion

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The effects of benzodiazepine agonists, inverse agonists and Ro 15–1788 on the responses of the superior cervical ganglion to GABA in vitro

Abstract: 1 The effects of benzodiazepines and their antagonists on the responses to y-aminobutyric acid (GABA) of the superior cervical ganglion of the rat were examined using extracellular recording.

Cited by 30 publications

References 29 publications

Acute and chronic effects of the benzodiazepine receptor ligand FG 7142: proconvulsant properties and kindling

Acute and chronic effects of the benzodiazepine receptor ligand FG 7142: proconvulsant properties and kindling

The effects of drugs acting at the GABAA‐receptor/ionophore after chemical kindling with the benzodiazepine receptor ligand FG 7142

Neurochemical evidence for a neuronal GABAergic system in the rat sympathetic superior cervical ganglion

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The effects of drugs acting at the GABA_A‐receptor/ionophore after chemical kindling with the benzodiazepine receptor ligand FG 7142