CLONING AND EXPRESSION OF A FUNCTIONAL SEROTONIN TRANSPORTER FROM RAT-BRAIN

SELECTIVE antagonism of serotonin (5-hydroxytryptamine, 5HT) and noradrenaline transport by antidepressants is a key element in the 'amine' hypothesis of affective disorders 1. Uptake 2,3 and/or transport sites 4-5 of 5HT have been reported to be reduced in platelets of patients suffering from depression and in post-mortem brain samples of depressed patients 6 and suicide victims 7. To date there has been little molecular information available on the structure and regulation of 5HT transporters. Using the polymerase chain reaction 8 with degenerate oligonucleotides 9 derived from two highly conserved regions of the transporters for noradrenaline 10 and gamma-aminobutyric acid 11 (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.