Long-term antidepressant treatment reduces neuronal responsiveness to flurazepam: an electrophysiological study in the rat.

Long-term administration of various types of antidepressant drugs has been recently reported to reduce the density of benzodiazepine receptors in the rat CNS. In the present study, using the microiontophoretic technique, the effect of flurazepam application on cholecystokinin-induced activation of hippocampal pyramidal neurons was assessed in rats treated with the antidepressants desipramine, trimipramine and citalopram, and the antipsychotic chlorpromazine, for 3 weeks. All 3 antidepressant drugs, but not chlorpromazine, reduced the efficacy of flurazepam. A two-week treatment with desipramine produced a similar effect, whereas a one-week treatment with this drug failed to alter the effect of flurazepam. These results constitute further evidence that long-term antidepressant treatment down-regulates benzodiazepine receptors.