Cardiovascular effects of intracerebroventricular GABA,glycine and muscimol in the rat |
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Authors: | Bengt Persson |
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Affiliation: | (1) Department of Pharmacology, University of Göteborg, Fack, S-40033 Göteborg, Sweden |
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Abstract: | Summary Intracerebroventricular (i.c.v.) injections of gammaaminobutyric acid (GABA, 125–2,000 g), glycine (250–2,000 g) and muscimol (0.5–4 g) caused dose-dependent reductions of blood pressure and heart rate in conscious rats. Low doses of muscimol (<0.12 g) were hypertensive. The cardiovascular depression induced by GABA was antagonized by bicuculline (3.5 mg/kg i.p.), while that induced by glycine was counteracted more effectively by strychnine (0.7 mg/kg i.v.) than by bicuculline. The cardiovascular response to GABA, but not to glycine, was potentiated by pretreatment with pentobarbitone (50 mg/kg i.p.). It was prolonged by diazepam (5 mg/kg i.p.) and aminooxyacetic acid (AOAA, 25 mg/kg i.p., 4h) but not by AOAA (1 h) or nipecotic acid (1–100 g i.c.v.). Following treatment with d-amphetamine (5 mg/kg i.p.) or reserpine (10 mg/kg i.p., 6h) the cardiovascular depression induced by GABA was attenuated. Propranolol (2.5+2.5 mg/kg i.v. + s.c.) or atropine (2 mg/kg i.v.) alone partially counteracted and in combination completely prevented the negative chronotropic response to GABA. Neither central noradrenaline depletion by means of -MMT (after carbidopa) and -MT nor pretreatment with phenoxybenzamine (20 g i.c.v.) influenced the response to GABA. The arterial hypotension induced by GABA was prolonged after a high dose of atropine (10 mg/kg i.v.) but appeared attenuated by a low dose (2 mg/kg i.v.) or by physostigmine (0.1 mg/kg i.v.). Central serotonergic activation by means of 5-hydroxytryptophan after benzerazid antagonized the cardiovascular actions of GABA. Spiroperidol (0.05 mg/kg i.v.) and apomorphine (1 mg/kg i.v.) did not affect the blood pressure reduction in response to GABA.It is concluded that i.c.v. GABA causes cardiovascular depression by activation of GABA receptors and that the response is mediated by the sympathetic and vagal systems. There were no indications for an involvement of central noradrenergic of dopaminergic mechanisms while a decreased central cholinergic and an increased serotonergic activity possibly contribute to the cardiovascular effects of GABA. |
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Keywords: | GABA Central control of blood pressure Glycine |
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