European Journal of Pharmacology, 57 (1979) 263--266 © Elsevier/North-Holland Biomedical Press
263
Short communication CLONIDINE MYDRIASIS IN THE RAT TSEGGAI GHEREZGHIHER and MICHAEL C. KOSS
Departments of Pharmacology and of Ophthalmology and McGee Eye Institute, University of Okhalahoma Health Sciences Center, P.O. Box 26901, Oklahoma City, Okla. 73190, U.S.A. Received 22 May 1979, accepted 12 June 1979 T. GHEREZGHIHER and M.C. KOSS, Clonidine mydriasis in the rat, European J. Pharmacol. 57 (1979) 263-266. Pupillary responses to clonidine (3--100 pg/kg, i.v.) and epinephrine (1--30 pg/kg, i.v.) were observed in anesthetized rats. Clonidine caused a dose-dependent ~ydriasis which was effectively antagonized by pretreatment with yohimbine (1.5 mg/kg, i.v.). Pretreatment with phentolamine (5 mg/kg, i.v.) was less effective in antagonizing this clonidine-induced mydriasis. Phenoxybenzamine (2 mg/kg, i.v.) was almost without effect. In contrast, both phentolamine and phenoxybenzamine blocked the pupillary dilation produced by epinephrine while yohimbine pretreatment resulted in no antagonism of epinephrine-induced mydriasis. These results suggest that clonidine-induced mydriasis in the rat is mediated by a central adrenergic inhibitory mechanism. Clonidine
Yohimbine
Phenoxybenzamine
1. Introduction Clonidine produces an apparently species pupillary dilation in cats and rats (Walland and Kobinger, 1971; Kobinger, 1973). Recent findings from this laboratory have demonstrated that the clonidine mydriasis observed in the cat is due entirely to CNS inhibition of parasympathetic tone to the iris. As this effect is antagonized by yohibmine, a central adrenergic inhibitory mechansim may be involved (Koss and San, 1976; Koss and Christensen, 1979; Koss, 1979). The present experiments were undertaken to determine whether a similar CNS mechanism might be responsible for the clonidine mydriasis observed in the rat.
Phentolamine
Pupillary dilation
inserted into either the left or right jugular vein. Pupillary responses were measured with a millimeter ruler (0.1 mm divisions) using an operation microscope with an internal light source. A green filter was utilized in order to increase the contrast of the iris as well as to reduce the degree of light-induced pupillary constriction. All observations were made under the same general lighting conditions. All drugs were dissolved in physiological saline and the doses are expressed in terms of their salts. Clonidine and epinephrine were administered at approximately 5 min intervals.
3. Results
2. Materials and methods
3.1. Pupillary dilation produced by clonidine and epinephrine
Adult male Sprague-Dawley rats (300-450 g) were anesthetized with sodium pentobarbital (60 mg/kg, i.p.) Drugs were administered intravenously by means of a catheter
Both clonidine (3--100pg/kg, i.v.) and epinephrine (1--30 #g/kg, i.v.) produced a dose-related pupiUary dilation when administered to anesthetized rats (fig. 1). At each
264
T. GHEREZGHIHER, M.C. KOSS
25
CLONIDINE
EPINEPHRINE
~f •
//
/
/
I'
i
7 i"
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#
.;"
1.5
#
.:"
-
263
Short communication CLONIDINE MYDRIASIS IN THE RAT TSEGGAI GHEREZGHIHER and MICHAEL C. KOSS
Departments of Pharmacology and of Ophthalmology and McGee Eye Institute, University of Okhalahoma Health Sciences Center, P.O. Box 26901, Oklahoma City, Okla. 73190, U.S.A. Received 22 May 1979, accepted 12 June 1979 T. GHEREZGHIHER and M.C. KOSS, Clonidine mydriasis in the rat, European J. Pharmacol. 57 (1979) 263-266. Pupillary responses to clonidine (3--100 pg/kg, i.v.) and epinephrine (1--30 pg/kg, i.v.) were observed in anesthetized rats. Clonidine caused a dose-dependent ~ydriasis which was effectively antagonized by pretreatment with yohimbine (1.5 mg/kg, i.v.). Pretreatment with phentolamine (5 mg/kg, i.v.) was less effective in antagonizing this clonidine-induced mydriasis. Phenoxybenzamine (2 mg/kg, i.v.) was almost without effect. In contrast, both phentolamine and phenoxybenzamine blocked the pupillary dilation produced by epinephrine while yohimbine pretreatment resulted in no antagonism of epinephrine-induced mydriasis. These results suggest that clonidine-induced mydriasis in the rat is mediated by a central adrenergic inhibitory mechanism. Clonidine
Yohimbine
Phenoxybenzamine
1. Introduction Clonidine produces an apparently species pupillary dilation in cats and rats (Walland and Kobinger, 1971; Kobinger, 1973). Recent findings from this laboratory have demonstrated that the clonidine mydriasis observed in the cat is due entirely to CNS inhibition of parasympathetic tone to the iris. As this effect is antagonized by yohibmine, a central adrenergic inhibitory mechansim may be involved (Koss and San, 1976; Koss and Christensen, 1979; Koss, 1979). The present experiments were undertaken to determine whether a similar CNS mechanism might be responsible for the clonidine mydriasis observed in the rat.
Phentolamine
Pupillary dilation
inserted into either the left or right jugular vein. Pupillary responses were measured with a millimeter ruler (0.1 mm divisions) using an operation microscope with an internal light source. A green filter was utilized in order to increase the contrast of the iris as well as to reduce the degree of light-induced pupillary constriction. All observations were made under the same general lighting conditions. All drugs were dissolved in physiological saline and the doses are expressed in terms of their salts. Clonidine and epinephrine were administered at approximately 5 min intervals.
3. Results
2. Materials and methods
3.1. Pupillary dilation produced by clonidine and epinephrine
Adult male Sprague-Dawley rats (300-450 g) were anesthetized with sodium pentobarbital (60 mg/kg, i.p.) Drugs were administered intravenously by means of a catheter
Both clonidine (3--100pg/kg, i.v.) and epinephrine (1--30 #g/kg, i.v.) produced a dose-related pupiUary dilation when administered to anesthetized rats (fig. 1). At each
264
T. GHEREZGHIHER, M.C. KOSS
25
CLONIDINE
EPINEPHRINE
~f •
//
/
/
I'
i
7 i"
:;
#
.;"
1.5
#
.:"
-
