Presynaptic alpha 2- and postsynaptic beta-adrenoceptor sensitivity in slices of rat neocortex after chronic treatment with various antidepressant drugs

A N Schoffelmeer, E M Hoorneman, P Sminia, A H Mulder

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The effect of chronic (4 weeks) treatment of rats with the antidepressant drugs desipramine, maprotiline, chlorimipramine, zimelidine or iprindol on the sensitivity of presynaptic alpha 2- and postsynaptic beta-adrenoceptors in neocortical slices was investigated. Acute (1 day) treatment with the antidepressants did not affect the efflux of cyclic-AMP induced by isoprenaline (1 microM) from neocortical slices, while after chronic treatment the efflux of cyclic AMP was consistently reduced. Following acute administration the electrically-evoked release of [3H]noradrenaline (NA) from radiolabelled cortical slices remained unchanged. Upon chronic treatment with desipramine the release of [3H]NA was enhanced by about 45%. In contrast, after chronic treatment with maprotiline or chlorimipramine the electrically-evoked release of [3H]NA was not affected, whereas release was even slightly reduced after chronic administration of zimelidine or iprindol. In all cases, however, a similar inhibitory effect of exogenous NA (0.1 microM) on the release of [3H]NA was found. These data indicate that the desensitization of postsynaptic beta-adrenoceptors in rat brain after chronic treatment with antidepressant drugs is not paralleled by a reduction of presynaptic alpha 2-adrenoceptor sensitivity.

Original languageEnglish
Pages (from-to)115-9
Number of pages5
JournalNeuropharmacology
Volume23
Issue number2A
Publication statusPublished - Feb 1984

Cite this

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title = "Presynaptic alpha 2- and postsynaptic beta-adrenoceptor sensitivity in slices of rat neocortex after chronic treatment with various antidepressant drugs",
abstract = "The effect of chronic (4 weeks) treatment of rats with the antidepressant drugs desipramine, maprotiline, chlorimipramine, zimelidine or iprindol on the sensitivity of presynaptic alpha 2- and postsynaptic beta-adrenoceptors in neocortical slices was investigated. Acute (1 day) treatment with the antidepressants did not affect the efflux of cyclic-AMP induced by isoprenaline (1 microM) from neocortical slices, while after chronic treatment the efflux of cyclic AMP was consistently reduced. Following acute administration the electrically-evoked release of [3H]noradrenaline (NA) from radiolabelled cortical slices remained unchanged. Upon chronic treatment with desipramine the release of [3H]NA was enhanced by about 45{\%}. In contrast, after chronic treatment with maprotiline or chlorimipramine the electrically-evoked release of [3H]NA was not affected, whereas release was even slightly reduced after chronic administration of zimelidine or iprindol. In all cases, however, a similar inhibitory effect of exogenous NA (0.1 microM) on the release of [3H]NA was found. These data indicate that the desensitization of postsynaptic beta-adrenoceptors in rat brain after chronic treatment with antidepressant drugs is not paralleled by a reduction of presynaptic alpha 2-adrenoceptor sensitivity.",
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author = "Schoffelmeer, {A N} and Hoorneman, {E M} and P Sminia and Mulder, {A H}",
year = "1984",
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language = "English",
volume = "23",
pages = "115--9",
journal = "Neuropharmacology",
issn = "0028-3908",
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Presynaptic alpha 2- and postsynaptic beta-adrenoceptor sensitivity in slices of rat neocortex after chronic treatment with various antidepressant drugs. / Schoffelmeer, A N; Hoorneman, E M; Sminia, P; Mulder, A H.

In: Neuropharmacology, Vol. 23, No. 2A, 02.1984, p. 115-9.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Presynaptic alpha 2- and postsynaptic beta-adrenoceptor sensitivity in slices of rat neocortex after chronic treatment with various antidepressant drugs

AU - Schoffelmeer, A N

AU - Hoorneman, E M

AU - Sminia, P

AU - Mulder, A H

PY - 1984/2

Y1 - 1984/2

N2 - The effect of chronic (4 weeks) treatment of rats with the antidepressant drugs desipramine, maprotiline, chlorimipramine, zimelidine or iprindol on the sensitivity of presynaptic alpha 2- and postsynaptic beta-adrenoceptors in neocortical slices was investigated. Acute (1 day) treatment with the antidepressants did not affect the efflux of cyclic-AMP induced by isoprenaline (1 microM) from neocortical slices, while after chronic treatment the efflux of cyclic AMP was consistently reduced. Following acute administration the electrically-evoked release of [3H]noradrenaline (NA) from radiolabelled cortical slices remained unchanged. Upon chronic treatment with desipramine the release of [3H]NA was enhanced by about 45%. In contrast, after chronic treatment with maprotiline or chlorimipramine the electrically-evoked release of [3H]NA was not affected, whereas release was even slightly reduced after chronic administration of zimelidine or iprindol. In all cases, however, a similar inhibitory effect of exogenous NA (0.1 microM) on the release of [3H]NA was found. These data indicate that the desensitization of postsynaptic beta-adrenoceptors in rat brain after chronic treatment with antidepressant drugs is not paralleled by a reduction of presynaptic alpha 2-adrenoceptor sensitivity.

AB - The effect of chronic (4 weeks) treatment of rats with the antidepressant drugs desipramine, maprotiline, chlorimipramine, zimelidine or iprindol on the sensitivity of presynaptic alpha 2- and postsynaptic beta-adrenoceptors in neocortical slices was investigated. Acute (1 day) treatment with the antidepressants did not affect the efflux of cyclic-AMP induced by isoprenaline (1 microM) from neocortical slices, while after chronic treatment the efflux of cyclic AMP was consistently reduced. Following acute administration the electrically-evoked release of [3H]noradrenaline (NA) from radiolabelled cortical slices remained unchanged. Upon chronic treatment with desipramine the release of [3H]NA was enhanced by about 45%. In contrast, after chronic treatment with maprotiline or chlorimipramine the electrically-evoked release of [3H]NA was not affected, whereas release was even slightly reduced after chronic administration of zimelidine or iprindol. In all cases, however, a similar inhibitory effect of exogenous NA (0.1 microM) on the release of [3H]NA was found. These data indicate that the desensitization of postsynaptic beta-adrenoceptors in rat brain after chronic treatment with antidepressant drugs is not paralleled by a reduction of presynaptic alpha 2-adrenoceptor sensitivity.

KW - Adrenergic alpha-Antagonists/pharmacology

KW - Animals

KW - Antidepressive Agents/pharmacology

KW - Cerebral Cortex/drug effects

KW - Cyclic AMP/biosynthesis

KW - Electric Stimulation

KW - Isoproterenol/pharmacology

KW - Male

KW - Norepinephrine/metabolism

KW - Rats

KW - Rats, Inbred Strains

KW - Receptors, Adrenergic, alpha/drug effects

KW - Receptors, Adrenergic, beta/drug effects

KW - Time Factors

M3 - Article

VL - 23

SP - 115

EP - 119

JO - Neuropharmacology

JF - Neuropharmacology

SN - 0028-3908

IS - 2A

ER -