Subsensitivity of serotonin receptors after long-term treatment of rats with fluoxetine.

Binding of [3H]-serotonin ([3H]5-hydroxytryptamine, [3H]5HT) to high and low affinity sites in brain membranes from frontal cortex was compared in rats fed control chow or fluoxetine (0.01%) containing chow. A reduction in the number of high affinity binding sites and in the affinity of the low affinity binding sites was observed after 2, 4 or 6 weeks. Reduction in the number of [3H]5HT binding sites was also observed in cerebral cortex of rats given fluoxetine by daily intraperitoneal injection for 4 or 6 weeks. Thus, long-term treatment with a selective inhibitor of serotonin uptake, fluoxetine, caused subsensitivity of 5HT receptors in frontal cortex and cerebral cortex of rat brain.