Modulation of rat brainα2- and β-adrenergic receptor sensitivity following long-term treatment with antidepressants

Asakura, Mikio; Takeuchi, Tohru; Hasegawa, Kanae

doi:10.1016/0006-8993(82)90212-8

Cited by 60 publications

(16 citation statements)

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“…The present findings are in general agreement with previous results, in so far as repeated administration of DMI or ECS has been shown to decrease presynaptic X2-adrenoceptor function (Tang et al, 1979;McMillen et al, 1980;Heal et al, 1981;1987a;Sugrue, 1983) and cortical f-adrenoceptor number (Bergstrom & Kellar, 1979a, b;Sellinger-Barnette et al, 1980;Asakura et al, 1982;Sugrue, 1982;1983;Stanford & Nutt, 1982;Stanford et al, 1983). Moreover, chronic ECS has previously been demonstrated to reduce cortical a2-adrenoceptors (Pilc & Vetulani, 1982;Stanford & Nutt, 1982;Heal et al, 1987a).…”

Section: Discussionsupporting

confidence: 93%

“…Moreover, chronic ECS has previously been demonstrated to reduce cortical a2-adrenoceptors (Pilc & Vetulani, 1982;Stanford & Nutt, 1982;Heal et al, 1987a). However, the literature concerning the effects of repeated DMI on C2-adrenoceptor binding is confficting with findings of a decrease (Heal et al, 1987a), an increase (Johnson et al, 1980;Asakura et al, 1982) and no change (Stanford et al, 1983;Sugrue, 1983). The reason for this discrepancy may be that the effect of DMI on cortical a2-adrenoceptors is relatively small.…”

Section: Discussionmentioning

confidence: 99%

“…The most widely studied and consistent effect of antidepressant treatment in animals is a decrease in the number of /I-adrenoceptors in the brain (Bergstrom & Kellar, 1979ab;Sellinger-Barnette et al, 1980;Asakura et al, 1982;Sugrue, 1982;Stanford & Nutt, 1982). However, presynaptic x2-adrenoceptor func-1 Author for correspondence.…”

Section: Introductionmentioning

confidence: 99%

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Sex‐related differences in central adrenergic function and responsiveness to repeated administration of desipramine or electroconvulsive shock

Heal

Bristow

Hurst

et al. 1989

British J Pharmacology

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1 Clonidine induces hypoactivity in rodents. Male rats were found to be markedly more susceptible to the sedative effects of this a2-adrenoceptor agonist than females. Thus to obtain identical hypoactivity responses for subsequent experiments, clonidine was administered to male and female rats at doses of 0.2 and 0.5 mg kg-1, respectively. 2 The clonidine-induced hypoactivity response of female rats was not affected by the oestrous cycle. 3 Repeated injection of desipramine (DMI; 5mg kg-1 b.d.) for up to 14 days progressively attenuated clonidine-induced hypoactivity in both male and female rats. However, in males the attenuation was more rapid in onset and a greater overall reduction was obtained. This a2-adrenoceptor-mediated response was also progressively reversed by repeated daily administration of an electroconvulsive shock (ECS; 110 V, 1 s). In this case, although the maximum decrease was greater in males, the time of onset was identical in both sexes.4 There were no sex-related differences in either the number or affinity of a2-and ,B-adrenoceptors in rat cortex. Cortical a2-adrenoceptors were decreased by 14 days of DMI injection or 10 days of ECS treatment (ECS x 10) and these effects were identical in both sexes. These receptors were not altered by 2 days administration of DMI or ECS. Cortical fi-adrenoceptors were reduced in male and female rats by 2 and 14 days of DMI injection and by ECS x 10, but not ECS x 2. 5 Viewed overall, the data show differences in a2-adrenoceptor function between the sexes, as determined by clonidine-induced hypoactivity and the responsiveness of this paradigm to repeated administration of DMI and ECS. In contrast, no differences were observed in complementary a2-and /-adrenoceptor binding experiments using rat cortical tissue.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

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Sex‐related differences in central adrenergic function and responsiveness to repeated administration of desipramine or electroconvulsive shock

Heal

Bristow

Hurst

et al. 1989

British J Pharmacology

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“…The scrutiny 01' the data suggests that if the treatment was short-lasting, for 4 to 7 days, usually an increase in the density of alpha2 adrenoceptors was observed (Asakura, Tsukamoto and Hasegawa 1982;Johnson, Reisine, Spotnitz, Wieeh, Ursillo and Yamamura 1982). The studies in which antidepressants were given for 2-3 weeks in most cases did not show any change in alpha2 adrenoceptor population (e.g., Sugrue 1981).…”

mentioning

confidence: 94%

Complex Action of Antidepressant Treatment on Central Adrenergic System: Possible Relevance to Clinical Effects

Vetulani¹

1984

Pharmacopsychiatry

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Chronic antidepressant treatment with classical and atypical antidepressant drugs and ECT leads to complex changes in the central adrenergic system, consisting of upregulation of alpha 1 and downregulation of alpha 2 and beta adrenoceptors. These changes may lead to a specific facilitation of neurotransmission in structures employing alpha 1 adrenoceptors, involved in the control of mood and emotions.

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“…This is understandable in light of the uncertain nature of the pathophysiology of depression, and the absence of animal models in which to study the disease and its response to therapy. The cyclic antidepressants have, in animal studies, been found to alter a number of neuronal adrenergic receptors and neurotransmitters (Asakura et al 1982;Heninger & Charney 1987;Richelson 1991;Salzman & van der Kolk 1984;Siever et al 1985).…”

Section: Pharmacologymentioning

confidence: 99%

Drug Therapy for Geriatric Depression

Bressler

Katz

1993

Drugs & Aging

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Depression is a common problem in elderly patients. The identification and treatment of depression may be more complex in older than in younger patients because of co-existing illnesses and concurrent drug therapy. In addition, a variety of medical conditions and drugs can cause depression. The pharmacology and pharmacokinetics of the cyclic antidepressants have been extensively studied. These agents are hepatically metabolised, often to an active agent. The clearance of the parent compound and the active metabolite(s) may be reduced in elderly patients, causing drug accumulation and increased toxicity. The cyclic antidepressants interact with a variety of neurotransmitters and their receptors. While these effects explain many of the adverse effects of the cyclic antidepressants, it is not clear whether the noradrenergic and serotoninergic effects of such drugs explain their antidepressant effects. Cyclic antidepressant therapy is associated with a variety of adverse effects, including sedation, anticholinergic effects and effects caused by alpha-adrenergic blockade. The cyclic antidepressants differ in their relative ability to cause these adverse effects. The newer cyclic antidepressants such as the selective serotonin reuptake inhibitors are relatively free of sedative and anticholinergic effects, but cause insomnia, nausea and possibly cardiac arrhythmias. All cyclic antidepressants appear to be equally effective. Therefore, the choice of a cyclic antidepressant for a specific patient must be based on several factors, including the risk of adverse effects. In elderly patients, the initial dose of cyclic antidepressants should be lower than the usual dose recommended for younger adults, and titrated slowly. All antidepressants require at least 2 to 3 weeks for their antidepressant effects to be seen. Because depression is a relapsing disease, maintenance antidepressant therapy may be indicated to reduce the risk of recurrent depression. The monoamine oxidase (MAO) inhibitors are effective antidepressants, especially in atypical depression. However, the adverse effects and risk of potentially lethal drug interactions of the older agents preclude their routine use. However, the new reversible MAO inhibitors may prove to be a well tolerated alternative in older patients. Antidepressant therapy should not be avoided simply because of a patient's age. However, the clinician must be conservative in the use of cyclic antidepressants in elderly patients and monitor closely for adverse drug reactions.

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Modulation of rat brainα2- and β-adrenergic receptor sensitivity following long-term treatment with antidepressants

Cited by 60 publications

References 11 publications

Sex‐related differences in central adrenergic function and responsiveness to repeated administration of desipramine or electroconvulsive shock

Sex‐related differences in central adrenergic function and responsiveness to repeated administration of desipramine or electroconvulsive shock

Complex Action of Antidepressant Treatment on Central Adrenergic System: Possible Relevance to Clinical Effects

Drug Therapy for Geriatric Depression

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