MODULATORY EFFECT OF ANTIDEPRESSANTS ON PERIPHERAL-TYPE BENZODIAZEPINE RECEPTORS

The effect of 21 days of imipramine hydrochloride (10 mg/kg) and phenelzine sulfate (10 mg/kg) administration followed by a 7-day period of withdrawal on peripheral-type benzodiazepine receptors was studied in male Sprague-Dawley rats. Both imipramine and phenelzine down-regulated adrenal peripheral-type benzodiazepine receptors (-18% P < 0.05; and -32%, P < 0.01, respectively) and up-regulated hepatic peripheral-type benzodiazepine receptors (+27%, P < 0.05; and +76%, P < 0.0001, respectively), while no alteration was observed in the kidney. Adrenal peripheral-type benzodiazepine receptors decreased further (-30% versus controls) after withdrawal from imipramine, while full restoration to normal values occurred following phenelzine withdrawal. [H-3]PK 11195 binding to the liver did not differ significantly from the control values after withdrawal from either drug. The observed changes can be explained as adaptive responses to antidepressant-induced hormonal and cellular alterations.