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CENTRAL AMINERGIC MECHANISMS ASSOCIATED WITH THE CLONIDINE WITHDRAWAL SYNDROME
Author(s) -
Lewis S.J.,
Fennessy M. R.,
Taylor D. A.
Publication year - 1981
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1981.tb00755.x
Subject(s) - clonidine , endocrinology , medicine , saline , serotonin , histamine , medulla oblongata , heart rate , catecholamine , anesthesia , chemistry , blood pressure , central nervous system , receptor
SUMMARY 1.Rats were injected twice daily, at 12.00 and 24.00 hours, with clonidine hydrochloride (50 μg/kg, i‐P‐) until they had received seven injections. Two hours after the 7th injection, their blood pressures, heart rates and body temperatures were decreased ( P <0.05) when compared to saline‐treated controls. 2. In rats which received six injections of clonidine hydrochloride (50 μg/kg, i.p.) and an injection of saline when the 7th injection of clonidine was due, the blood pressure, heart rate and body temperature were all significantly ( P <0.05) increased 2 h after the saline injection, which was 14 h after the 6th injection of clonidine. 3. Chronic treatment with clonidine hydrochloride significantly ( P <0.05) increased the concentrations of noradrenaline and decreased those of histamine in the medulla oblongata/pons. In the hypothalamus the concentrations of noradrenaline and serotonin were significantly ( P <0.05) increased. 4. During the withdrawal phase the concentrations of dopamine and histamine were significantly ( P <0.05) increased in the medulla oblongata/pons, while those of noradrenaline had returned to the control values. In the hypothalamus the concentrations of histamine and noradrenaline were significantly ( P <0.05) increased while those of serotonin had returned to the control value. 5. Methysergide (2 mg/kg, i.p.) when injected during the withdrawal phase produced significant ( P <0.05) reductions in the hypertension, tachycardia and hyperthermia which are displayed at this time. 6. It is concluded that chronic clonidine treatment may decrease the release of noradrenaline from the medulla oblongata/pons and that of serotonin from the hypothalamus. However, on cessation of treatment, increases in the release of these amines appear to be associated with the increases in blood pressure, heart rate and body temperature.