Chronic treatment with amitriptyline produces subsensitivity to the hypothermic effects of clonidine

Abstract

1. Supersensitivity or up-regulation of presynaptic alpha 2-adrenoceptors may be involved in the pathogenesis of depression. 2. The authors used a thermoregulation paradigm to test the hypothesis that chronic treatment with a tricyclic antidepressant amitriptyline (AMI) produces subsensitivity to the hypothermic effects of the alpha 2 agonist clonidine. 3. Treatment with amitriptyline produced blunting of the hypothermic response to clonidine. 4. Subsensitivity persisted for at least 21 days--that point after the discontinuation of the tricyclic at which the animals were last challenged with clonidine. 5. These findings are consistent with previous reports that tricyclic antidepressants produce subsensitivity of alpha 2 adrenoceptors.

Alpha-2 adrenergic-induced changes in rectal temperature in adult and 13-day old rats following acute and repeated desipramine administration

“…An enhanced hypothermic effect has been observed when guanfacine is used to decrease temperature after 21 days of desipramine treatment, but an attenuation of the hypothermic response when clonidine was used as the agonist [ 12 ]. Others have also reported an attenuation of the clonidine-induced hypothermic effect 24 h after repeated treatment with desipramine [ 12 , 25 ], imipramine [ 19 , 26 ] and amitripyline [ 27 , 28 ]. These results suggest that the effects of desipramine on drug-induced hypothermic response may depend on the agonist used, the receptors that are activated, and/or the extent of receptor activation.…”

Alpha-2 adrenergic-induced changes in rectal temperature in adult and 13-day old rats following acute and repeated desipramine administration

“…An enhanced hypothermic effect has been observed when guanfacine is used to decrease temperature after 21 days of desipramine treatment, but an attenuation of the hypothermic response when clonidine was used as the agonist [ 12 ]. Others have also reported an attenuation of the clonidine-induced hypothermic effect 24 h after repeated treatment with desipramine [ 12 , 25 ], imipramine [ 19 , 26 ] and amitripyline [ 27 , 28 ]. These results suggest that the effects of desipramine on drug-induced hypothermic response may depend on the agonist used, the receptors that are activated, and/or the extent of receptor activation.…”

Pharmacokinetic-Pharmacodynamic Modeling of Buspirone and Its Metabolite 1-(2-Pyrimidinyl)-piperazine in Rats

“…Furthermore its effect can be antagonized by selective 5-HT 1A receptor antagonists (Koenig et al, 1988;Cryan et al, 1999) and its selectivity over other receptors that may also mediate a hypothermic response, e.g., the ␣ 2 -AR (Dilsaver et al, 1989;MacDonald et al, 1989), -opioid (OP3) (Spencer et al, 1988), dopamine D 3 (Barik and de Beaurepaire, 1998) and adenosine A 1 receptors (Malhotra and Gupta, 1997) is high (New, 1990;Gobert et al, 1995). 1-PP on the other hand has affinity for both the 5-HT 1A (K D ϭ 1035 nM ϭ 94 ng/ml) and the ␣ 2 -AR (K D ϭ 40 nM ϭ 3.6 ng/ml) (Gobert et al, 1995).…”

Conversion of Elderly to Alzheimer's Dementia: Role of Confluence of Hypothermia and Senescent Stigmata – the Plausible Pathway

“…However, the alpha 1-adrenoceptor antagonist, prazosin, and the 5-HT receptor antagonist, metergoline, significantly enhanced the hypothermic effects of caffeine in mice [31]. The alpha 2 agonist, e.g., clonidine, causes hypothermic effects [28], as does the alpha 2 antagonist yohimbine [27]. Administration of beta-adrenergic isoproterenol 10 min after treatment with either ethanol or saline was accompanied by an increase in the metabolic rates of both groups, although the magnitude of the increase in the ethanol-treated group was less than that of controls.…”

“…The withdrawal of tricyclic antidepressants produces symptoms characteristic of cholinergic overdrive. Treatment with amitriptyline resulted in marked enhancement of the cholinomimetic-induced hypothermia [27,28].…”

Alpha-2 adrenergic-induced changes in rectal temperature in adult and 13-day old rats following acute and repeated desipramine administration

“…An enhanced hypothermic effect has been observed when guanfacine is used to decrease temperature after 21 days of desipramine treatment, but an attenuation of the hypothermic response when clonidine was used as the agonist [ 12 ]. Others have also reported an attenuation of the clonidine-induced hypothermic effect 24 h after repeated treatment with desipramine [ 12 , 25 ], imipramine [ 19 , 26 ] and amitripyline [ 27 , 28 ]. These results suggest that the effects of desipramine on drug-induced hypothermic response may depend on the agonist used, the receptors that are activated, and/or the extent of receptor activation.…”

Pharmacokinetic-Pharmacodynamic Modeling of Buspirone and Its Metabolite 1-(2-Pyrimidinyl)-piperazine in Rats

“…Furthermore its effect can be antagonized by selective 5-HT 1A receptor antagonists (Koenig et al, 1988;Cryan et al, 1999) and its selectivity over other receptors that may also mediate a hypothermic response, e.g., the ␣ 2 -AR (Dilsaver et al, 1989;MacDonald et al, 1989), -opioid (OP3) (Spencer et al, 1988), dopamine D 3 (Barik and de Beaurepaire, 1998) and adenosine A 1 receptors (Malhotra and Gupta, 1997) is high (New, 1990;Gobert et al, 1995). 1-PP on the other hand has affinity for both the 5-HT 1A (K D ϭ 1035 nM ϭ 94 ng/ml) and the ␣ 2 -AR (K D ϭ 40 nM ϭ 3.6 ng/ml) (Gobert et al, 1995).…”

Conversion of Elderly to Alzheimer's Dementia: Role of Confluence of Hypothermia and Senescent Stigmata – the Plausible Pathway

“…However, the alpha 1-adrenoceptor antagonist, prazosin, and the 5-HT receptor antagonist, metergoline, significantly enhanced the hypothermic effects of caffeine in mice [31]. The alpha 2 agonist, e.g., clonidine, causes hypothermic effects [28], as does the alpha 2 antagonist yohimbine [27]. Administration of beta-adrenergic isoproterenol 10 min after treatment with either ethanol or saline was accompanied by an increase in the metabolic rates of both groups, although the magnitude of the increase in the ethanol-treated group was less than that of controls.…”

“…The withdrawal of tricyclic antidepressants produces symptoms characteristic of cholinergic overdrive. Treatment with amitriptyline resulted in marked enhancement of the cholinomimetic-induced hypothermia [27,28].…”

Alpha-2 adrenergic-induced changes in rectal temperature in adult and 13-day old rats following acute and repeated desipramine administration

“…An enhanced hypothermic effect has been observed when guanfacine is used to decrease temperature after 21 days of desipramine treatment, but an attenuation of the hypothermic response when clonidine was used as the agonist [ 12 ]. Others have also reported an attenuation of the clonidine-induced hypothermic effect 24 h after repeated treatment with desipramine [ 12 , 25 ], imipramine [ 19 , 26 ] and amitripyline [ 27 , 28 ]. These results suggest that the effects of desipramine on drug-induced hypothermic response may depend on the agonist used, the receptors that are activated, and/or the extent of receptor activation.…”

Pharmacokinetic-Pharmacodynamic Modeling of Buspirone and Its Metabolite 1-(2-Pyrimidinyl)-piperazine in Rats

“…Furthermore its effect can be antagonized by selective 5-HT 1A receptor antagonists (Koenig et al, 1988;Cryan et al, 1999) and its selectivity over other receptors that may also mediate a hypothermic response, e.g., the ␣ 2 -AR (Dilsaver et al, 1989;MacDonald et al, 1989), -opioid (OP3) (Spencer et al, 1988), dopamine D 3 (Barik and de Beaurepaire, 1998) and adenosine A 1 receptors (Malhotra and Gupta, 1997) is high (New, 1990;Gobert et al, 1995). 1-PP on the other hand has affinity for both the 5-HT 1A (K D ϭ 1035 nM ϭ 94 ng/ml) and the ␣ 2 -AR (K D ϭ 40 nM ϭ 3.6 ng/ml) (Gobert et al, 1995).…”

Conversion of Elderly to Alzheimer's Dementia: Role of Confluence of Hypothermia and Senescent Stigmata – the Plausible Pathway

“…However, the alpha 1-adrenoceptor antagonist, prazosin, and the 5-HT receptor antagonist, metergoline, significantly enhanced the hypothermic effects of caffeine in mice [31]. The alpha 2 agonist, e.g., clonidine, causes hypothermic effects [28], as does the alpha 2 antagonist yohimbine [27]. Administration of beta-adrenergic isoproterenol 10 min after treatment with either ethanol or saline was accompanied by an increase in the metabolic rates of both groups, although the magnitude of the increase in the ethanol-treated group was less than that of controls.…”

“…The withdrawal of tricyclic antidepressants produces symptoms characteristic of cholinergic overdrive. Treatment with amitriptyline resulted in marked enhancement of the cholinomimetic-induced hypothermia [27,28].…”