Effect of sertraline treatment on benzodiazepine receptors in the rat brain

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Abstract
Summary In this paper we describe the modification of benzodiazepine (BDZ) binding sites in the rat brain after different times of treatment with the 5-hydroxytryptamine-(5HT) uptake blocker sertraline. We investigated the effect of 8, 15 and 30 days sertraline treatment (10 mg/kg/day, i.p.) on3H-flunitrazepam binding sites. In order to describe the anatomical site of action of the drug, the experiment has been carried out by means of quantitative receptor autoradiography. After 8 days of sertraline treatment, an increase of BDZ receptor density is found in the olfactory tubercle. This effect is reversed at 15 and 30 days. At 15 days of treatment, an increase is found in the anterior cingulate cortex. This increase is still present after 30 days of treatment. At 30 days of treatment, we also found an increase of BDZ receptor density in the frontoparietal motor cortex and in the septal nuclei. The Scatchard plots obtained from the saturation experiments indicate that this increase of the receptor density is due to an increase of both the receptor number and affinity. All the other investigated areas are unaffected by the sertraline treatment. The possible neurochemical basis of these BDZ receptor regulation by sertraline and its influence in the therapeutical profile are discussed.