Chronic Treatment with Antidepressant Drugs and ECT Differentially Modifies the Hypothermic Action of Clonidine and Guanfacine

Abstract

The hypothermia inducing action of clonidine and guanfacine was abolished by yohimbine and idazoxan pretreatment which suggests an alpha 2-adrenoceptor involvement in this effect. The effects of acute and chronic treatment with the antidepressant drugs desipramine (DMI), amitriptyline (AMI), maprotiline (MAP), mianserin (MIAN), iprindol (IPR), alaproclate (ALA) and electroconvulsive treatment (ECT) on the hypothermic action of the alpha 2-adrenoceptor agonists clonidine and guanfacine were studied. Acute administration of MIAN potentiated clonidine induced hypothermia whereas acute MIAN, IPR and ALA potentiated guanfacine induced hypothermia. Repetitive DMI, AMI and MAP treatment attenuated clonidine-induced hypothermia whereas guanfacine-induced hypothermia was potentiated by chronic treatment with DMI, AMI, MAP and MIAN, ECT applied without anaesthesia attenuated both clonidine and guanfacine hypothermia, however, under ethyl ether anaesthesia ECT was effective only towards guanfacine hypothermia. This discrepancy is discussed in terms of the relative selectivity of the agonists used, the reliability of agonist studies for indexing receptor function, and possible pharmacokinetic interaction.

Adaptive Changes in α‐2 Adrenoceptor Mediated Responses: Analgesia, Hypothermia and Hypoactivity

“…This evidence fits the hypothesis of a-Zadrenoceptor down-regulation after chronic treatment with antidepressant drugs (Vetulani 1984;Kostowski et al 1986). Interestingly, the hypothermic and sedative effects of guanfacine were potentiated whereas the analgesic action was attenuated after chronic DMI treatment, the hypothermia result being in line with a previous report (Danysz et al 1987). However, as shown in the present paper it parallels the other functional effects.…”

“…We were not aware of any reports concerning the influence of chronic treatment with DMI on the analgesic action of clonidine. This discrepancy is difficult to explain, it may be due to some pharmacokinetic interaction, but the fact that not all guanfacine actions were regulated the same direction argues against this hypothesis (see Danysz et al 1987 for discussion). Interestingly, the hypothermic and sedative effects of guanfacine were potentiated whereas the analgesic action was attenuated after chronic DMI treatment, the hypothermia result being in line with a previous report (Danysz et al 1987).…”

“…before saline [A], clonidine (0.2 mg/kg)[B] or hypothermic effects, Luttinger et alDanysz et al 1987). 6.…”

Chronic oral nicotine increases brain [3H]epibatidine binding and responsiveness to antidepressant drugs, but not nicotine, in the mouse forced swim test

“…Chronic administration of SSRI antidepressants is associated with blunted hypothermic responses to agonists at the inhibitory 5-HT 1A receptor in rodents (Cryan et al 1998;Hensler et al 1991). Similarly, chronic NRI treatment attenuates the hypothermic response to α 2 -adrenoceptor agonists (Bill et al 1989;Danysz et al 1987). Furthermore, chronic antidepressant treatment is accompanied by decreased expression levels of the transporters for 5-HT (SERT; Benmansour et al 1999;Mirza et al 2007;Troelsen et al 2005) and NE (NET; Bauer and Tejani-Butt 1992;Benmansour et al 2004;Troelsen et al 2005).…”

“…Furthermore, chronic antidepressant treatment is accompanied by decreased expression levels of the transporters for 5-HT (SERT; Benmansour et al 1999;Mirza et al 2007;Troelsen et al 2005) and NE (NET; Bauer and Tejani-Butt 1992;Benmansour et al 2004;Troelsen et al 2005). We therefore investigated whether chronic nicotine treatment had any effects on the hypothermic response to the 5-HT 1A agonist, 8-OH-DPAT (Cryan et al 1998;Hensler et al 1991), and the α 2 -adrenoceptor agonist, clonidine (Bill et al 1989;Danysz et al 1987), assays often employed to investigate the functionality of these receptors. In keeping with our hypothesis, we also measured levels of [ 3 H]citalopram and [ 3 H]nisoxetine binding to determine possible changes in SERT and NET expression levels, respectively.…”