PHARMACOLOGICAL CHARACTERIZATION OF SEROTONIN SYNTHESIS AND UPTAKE SUGGEST A FALSE TRANSMITTER ROLE FOR SEROTONIN IN THE PITUITARY INTERMEDIATE LOBE

A subpopulation of nerve fibers in the rat pituitary intermediate lobe (IL) have been shown to exhibit colocalization of serotonin (5-HT-IR) and tyrosine hydroxylase immunoreactivities and they are sensitive to neurotoxins specific to catecholamine neurons. This study was set out to examine the uptake and synthesis mechanisms of serotonin in these fibers. We developed an in vitro technique in which the neurointermedi ate lobe explants were incubated (14 and 48 h) in the presence of vari ous drugs and serotonin was subsequently visualized by immunohistochem istry. Control incubation in the presence of serotonin (10(-6) M) resu lted in a rich plexus of 5-HT-IR fibers in both posterior and intermed iate lobes. Fluoxetine and citalopram (10(-6) M and 10(-5) M), inhibit ors of 5-HT transporter, did not affect 5-HT-IR in the IL fibers, unle ss they were used in concentrations high enough (10(-4) M and 10(-3) M ) to block unspecifically a number of monoamine transporters. The same applied for desipramine (10(-5)-10(-7) M), an inhibitor of the noradr enaline transporter. However, cocaine (10(-5)-10(-6) M) blocked seroto nin uptake into these terminals, suggesting that serotonin uptake occu rs through a dopamine transporter. Incubation of the IL in presence of L-tryptophan (10(-4) M) did not result in 5-HT-IR in the IL fibers sh owing colocalization of 5-HT-IR and tyrosine hydroxylase, which sugges ts that these fibers do not synthesize serotonin. The present results suggest that serotonin is taken up into the IL terminals by a dopamine transporter and is not synthesized in them, at least in vitro. Thus, serotonin may act as a false transmitter in some of the IL fibers, whi ch may prove to be a valuable model tissue for studying serotonin's ro le as an exogenously synthesized cotransmitter.