[3H]adrenaline release from hypothalamic synaptosomes and its modulation by clonidine: effects of chronic antidepressant drug regimens.
[3H]Adrenaline ([3H]ADR, 40 nM) was accumulated by rat hypothalamic synaptosomes (P2) more rapidly and in significantly greater amounts than by similar preparations from cerebral cortex. There was no significant difference between these two tissues in the rate or amount of [3H]noradrenaline ([3H]NA, 40 nM) accumulation. Talusupram (10 microM), maximally inhibited the uptake of [3H]ADR into hypothalamic synaptosomes by 60%. Nomifensine further inhibited uptake by 14%. From these observations it was concluded that some [3H]ADR was accumulated into non adrenergic neuronal terminals. The effects of desipramine (DMI, 10 mg/kg/day and clorgyline (1 mg/kg/day) administration for 28 days on K+-evoked release of [3H]ADR was investigated using superfused hypothalamic synaptosomes. After both chronic antidepressant drug regimens, total [3H]ADR release (spontaneous + evoked) was significantly reduced. Evoked release of [3H]ADR (by KCl, 16 mM) was significantly reduced after the DMI but not the clorgyline regimens. Presynaptic alpha 2-adrenoceptor function in the hypothalamus was assessed during superfusion by measuring the reduction in K+-evoked release of [3H]ADR caused by clonidine (1 microM). The attenuating effects of clonidine on [3H]ADR release (42% in untreated controls and 36% after chronic clorgyline) was diminished (to 4%) after chronic DMI administration. Alpha 2 adrenoceptor numbers in the rat hypothalamus were not significantly changed after clorgyline or DMI administration, suggesting that the functional subsensitivity seen in synaptosomes after DMI, may not be related to alpha 2 adrenoceptor down regulation.
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003000:Clonidine / Q000494:pharmacology*; D003010:Clorgyline / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004837:Epinephrine / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism*
D000928:Antidepressive Agents; D011942:Receptors, Adrenergic, alpha; D003010:Clorgyline; D003000:Clonidine; D003891:Desipramine; D009638:Norepinephrine; D004837:Epinephrine