Cloning and expression of a functional serotonin transporter from rat brain

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Abstract
SELECTIVE antagonism of serotonin (5-hydroxytryptamine, 5HT) and noradrenaline transport by antidepressants is a key element in the 'amine' hypothesis of affective disorders1. Uptake2,3 and/or transport sites4,5 of 5HT have been reported to be reduced in platelets of patients suffering from depression and in post-mortem brain samples of depressed patients6 and suicide victims7. To date there has been little molecular information available on the structure and regulation of 5HT transporters. Using the polymerase chain reaction8with degenerate oligonucleotides9 derived from two highly conserved regions of the transporters for noradrenaline10 and γ-aminobutyric acid11(GABA), we have identified a large family of related gene products expressed in rodent brain. One of these products hybridizes to a single 3.7-kilobase RNA restricted to rat midbrain and brainstem, where it is highly enriched within the serotonergic raphe complex. Transfection with a single 2.3-kilobase brainstem complementary DNA clone is sufficient to confer expression of a Na+-dependent 5HT transporter upon non-neural cells, with transport selectively and potently antagonized by 5HT uptake-specific antidepressants, including paroxetine, citalopram and fluoxetine.