Chronic administration of antidepressant drugs increases the density of cortical [3H]prazosin binding sites in the rat

We found previously that the beta-agonist clenbuterol and the alpha-agonist clonidine produced hyperthermia in rats kept at high ambient temperature, which effects were mediated by beta- and alpha 2-adrenoceptors, respectively. In the present paper this observation was used for testing the responsiveness of beta- or alpha 2-adrenoceptors, changed by a pharmacological manipulation, i.e., by chronic treatment with antidepressants. The animals were pretreated with desipramine, imipramine or amitriptyline twice a day for 1 or 2 weeks. All antidepressants significantly attenuated the clenbuterol-induced hyperthermia after 2 weeks of treatment. The effect of desipramine was stronger than that of the other antidepressants and appeared as little as 1 week after the treatment. The hyperthermic effect of clonidine was significantly reduced by repeated treatment with desipramine, increased after 2 weeks administration of imipramine, whereas amitriptyline produced no significant changes. In conclusion, these data suggest that, after repeated treatment, the antidepressants tested produce an adaptive decrease in function of beta-adrenoceptors while the same drugs exert differential effects on alpha 2-receptors. Moreover, clenbuterol induced hyperthermia may be a useful test for examining possible functional changes in beta-adrenoceptor sensitivity.

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“…An increased 3H-prazosin binding was found after chronic IMI administration (Campbell and McKerman, 1982;Vetulani et al, 1984).…”

Section: Discussionmentioning

confidence: 95%

Adaptive and differential changes on ?- and ?2-adrenoreceptors mediated hyperthermia after chronic treatment with antidepressant drugs in the rat kept at high ambient temperature

Mogilnicka

Klimek

Nowak

et al. 1985

J. Neural Transmission

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“…While the effects of DMI on a.,-receptors in rat brain are controversial (Green, 1990) there are several reports of in- (Rehavi et al, 1980;Cohen et al, 1982;Menkes et al, 1983;Vetulani et al, 1984;Maj et al, 1985;Nowak & Przegalinski, 1988). In addition, there is some behavioural evidence for a functional supersensitivity in treated animals (Davis et al, 1981;Plaznik & Kostowski, 1985;Mogilnicka et al, 1987).…”

Section: Discussionmentioning

confidence: 99%

Neuroendocrine response to clonidine and 8‐OH‐DPAT in rats following chronic administration of desipramine or sertraline

O’Donnell

Grealy

1992

British J Pharmacology

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1 Rats were administered either desipramine (DMI) or sertraline daily at doses 7.5 mg kg-' or 10mg kg-', i.p., respectively and the effects on the functional state of hypothalamic neuroendocrine control mechanisms assessed by measurements of plasma hormones following acute drug challenge. The effects of treatment on gross behaviour and brain adrenoceptor density were also determined. 2 Both DMI and sertraline caused significant reduction in activity measured as ambulation and rearing at 14 days of treatment. 3 All animals were chronically cannulated after 14 days of treatment and tested for neuroendocrine response to acute i.v. clonidine (50 lgkg-') or 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 250 gkg-') after 21 or more days of treatment. 4 Rats treated with DMI but not sertraline showed a virtually complete suppression of the growth hormone (GH) secretion elicited by clonidine in controls, while the secretion of corticosterone was augmented. 5 Treatment with DMI but not sertraline led to a significantly greater 8-OH-DPAT-induced secretion of prolactin than in the control rats, while the plasma concentrations of corticosterone following 8-OH-DPAT were not influenced by either DMI or sertraline treatment. 6 The density (but not the affinity) of cerebral cortical binding of [3H]-dihydroalprenolol was significantly reduced by DMI treatment. 7 These results show that DMI treatment blunted the sensitivity of post-synaptic a2-adrenoceptors, accompanied by complex interactions manifested as increased responsiveness of a,-adrenoceptors and 5-HTA receptors. Sertraline had no significant neurendocrine effects at a dose which significantly reduced gross activity.

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“…[3H]-WB-4101 binding) (Wetzel et al, 1981), this has not been consistently reproduced in other tissues, including the central nervous system (Vetulani et al, 1984;Kendall & Nahorski, 1985;Newman & Lerer, 1988;Salles et al, 1989). Various factors affecting the concentration of noradrenaline in the synaptic cleft may account for these differences between tissues, and the smooth muscle of the rat vas deferens has the densest innervation and probably the narrower synaptic cleft (10-30 nm) (Furness & Iwajama, 1971), as compared to other noradrenergically innervated tissues.…”

Section: Adaptation Of A-adrenoceptors In Rat Vas Deferens 681mentioning

confidence: 99%

Modulation of α₁‐adrenoceptors and functional consequences in the bisected rat vas deferens following chronic inhibition of neuronal noradrenaline uptake

Sallés

Badı́a

1993

British J Pharmacology

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reduction in density of a,-adrenoceptors was higher in the epididymal than the prostatic half. Desipramine reduced the B. only in the epididymal portion. 5 These results indicate that differential regulation of ax-adrenoceptors in either portion of the rat vas deferens could result from a greater degree of activation of these receptors in the epididymal half after chronic inhibition of neuronal noradrenaline uptake. The different functional consequences of the loss of al-adrenoceptors in each portion seems to be explained on the basis of a different relationship between the occupancy of the receptor and the response elicited.

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Chronic administration of antidepressant drugs increases the density of cortical [3H]prazosin binding sites in the rat

Cited by 65 publications

References 14 publications

Adaptive and differential changes on ?- and ?2-adrenoreceptors mediated hyperthermia after chronic treatment with antidepressant drugs in the rat kept at high ambient temperature

Adaptive and differential changes on ?- and ?2-adrenoreceptors mediated hyperthermia after chronic treatment with antidepressant drugs in the rat kept at high ambient temperature

Neuroendocrine response to clonidine and 8‐OH‐DPAT in rats following chronic administration of desipramine or sertraline

Modulation of α₁‐adrenoceptors and functional consequences in the bisected rat vas deferens following chronic inhibition of neuronal noradrenaline uptake

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Chronic administration of antidepressant drugs increases the density of cortical [3H]prazosin binding sites in the rat

Cited by 65 publications

References 14 publications

Adaptive and differential changes on ?- and ?2-adrenoreceptors mediated hyperthermia after chronic treatment with antidepressant drugs in the rat kept at high ambient temperature

Adaptive and differential changes on ?- and ?2-adrenoreceptors mediated hyperthermia after chronic treatment with antidepressant drugs in the rat kept at high ambient temperature

Neuroendocrine response to clonidine and 8‐OH‐DPAT in rats following chronic administration of desipramine or sertraline

Modulation of α1‐adrenoceptors and functional consequences in the bisected rat vas deferens following chronic inhibition of neuronal noradrenaline uptake

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Modulation of α₁‐adrenoceptors and functional consequences in the bisected rat vas deferens following chronic inhibition of neuronal noradrenaline uptake