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.
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects*; D000242:Cyclic AMP / Q000096:biosynthesis; D004558:Electric Stimulation; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013997:Time Factors
chemical_list: D000317:Adrenergic alpha-Antagonists; D000928:Antidepressive Agents; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D007545:Isoproterenol; D009638:Norepinephrine