European Journal of Pharmacology, 80 (i 982) 109-113 109 Elsevier Biomedical Press DEPRESSION BY CHRONIC ELECTROCONVULSIVE TREATMENT OF CLONIDINE HYPOTHERMA AND [3H]CLONIDINE BINDING TO RAT CORTICAL MEMBRANES ANDRZEJ PILC and JERZY VETULANI * Department of Biochemistry, Institute of Pharmacology, Polish Academy of Sciences, Smetna Str. 12, 31-343 Krak~w, Poland Received 23 February 1982, accepted 8 March 1982 A. PILC and J. VETU LANI, Depression by chronic electroconvulsive treatment of clonidine hypothermia and [3H ]clonidine binding to rat cortical membranes, European J. Pharmacol. 80 (1982) 109-113. The effects of chronic electroconvulsive treatment (ECT) on the binding of [3H]clonidine and on clonidine-induced hypothermia were studied in the rat. After 10 consecutive daily treatments we observed a reduction in the hypothermic action of clonidine and a loss of the high affinity binding sites of clonidine, without changes of the low affinity binding sites. The present results are indicative of the down-regulation of a2-adrenoceptors during chronic antidepressive treatment. Electroconvulsive treatment a2-Adrenoceptor [ 3H]Clonidine binding Clonidine hypothermia 1. Introduction From the beginnings of psychopharmacology the mode of action of antidepressant treatments has been associated with their influence on the noradrenergic system (Schildkraut, 1965). The best established common effect of a variety of antide- pressant treatments is the down-regulation of the fl-adrenoceptor, observed as a hyposensitivity of the noradrenergic cyclic AMP generating system (Vetulani and Sulser, 1975) and the depression of fl-adrenoceptor density (Wolfe et al., 1978). Recently, it has been found that chronic antide- pressant treatments may also affect noradrenergic a-receptors, as they attenuate the behavioural ef- fects of clonidine (Spyraki et al., 1981; Von Voigtlander et al., 1978) and reduce the density of [3H]clonidine binding sites (Smith et al., 1981; Vetulani et al., 1980). The present study was aimed at demonstrating the effect of chronic electroconvulsive treatment (ECT) on the a2-noradrenergic receptor as re- vealed by studies of clonidine-induced hypother- mia and [3H]clonidine binding to cortical mem- branes of the rat. * To whom all correspondence should be addressed. 0014-2999/82/0000-0000/$02.75 © 1982 Elsevier Biomedical Press 2. Materials and methods 2.1. Animals Male Wistar rats weighing 150-200 g were used. They were handled once a day for ten consecutive days; the handling included the attachment of clip electrodes to the ears. At the end of each handling the group subjected to ECT received an electric shock (150 mA, 50 Hz, 400 ms) through the electrodes. The shock invariably produced tonic extension of the hind limbs. 2.2. Testing of clonidine-induced hypothermia Clonidine (hydrochloride, Boehringer Sohn, In- gelheim) was given in a dose of 100 /~g/kg i.p., 24 h after the last handling. The oesophagal tem- perature was measured immediately before the injection and then at 30 min intervals for 2 h. 2.3. Measurement of [~H] clonidine binding The cerebral cortex was excised on an ice-cold plate from the brains of rats decapitated 24 h after the last handling, and stored under solid CO2 until used. The tissue was homogenized in 20 vol of