Acute and chronic effects of antidepressant drugs on β‐adrenergic function in astrocytes in primary cultures: An indication of glial involvement in affective disorders?

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Abstract
Acute and chronic effects of the antidepressant drugs tranylcypromine, a monoamine oxidase inhibitor, and amitriptyline, a monoamine uptake inhibitor, were studied on β‐adrenergic receptor function in mouse astrocytes in primary cultures. In clinically relevant concentrations, acute administration of either antidepressant drug had a direct inhibitory effect on the binding of the β‐adrenergic ligand dihydroalprenolol and on the isoproterenol‐induced accumulation of cyclic AMP. However, in the absence of isoproterenol, these drugs enhanced the formation of cyclic AMP in the astrocytes. Chronic exposure to amitriptyline or tranylcypromine led to a decrease in isoproterenol‐induced accumulation of cyclic AMP, and the time course for the development of this phenomenon was similar to that reported for whole brain in vivo. These findings suggest that these antidepressant drugs act as partial agonists at β‐adrenergic receptors on astrocytes, and that the down‐regulation of β‐adrenergic activity that occurs in vivo after chronic administration of antidepressant drugs may, to a large extent, take place in astrocytes and may result from the partial /3‐agonist nature of the drugs.