THE EFFECT OF UNILATERAL NEUROTOXIC LESIONS TO SEROTONIN FIBERS IN THE MEDIAL FOREBRAIN-BUNDLE ON THE METABOLISM OF [H-3] DOPA IN THE TELENCEPHALON OF THE LIVING RAT

We used quantitative autoradiography to measure the contribution of th e 5-hydroxytryptamine (5-HT, serotonin) innervation of rat telencephal on to the synthesis of dopamine (DA) from exogenous L-DOPA. One week a fter stereotaxic infusions of 5,7-dihydroxytryptamine (5,7-DHT, 1.6 mu g) into the right medial forebrain bundle (MFB), rats received [H-3]D OPA (200 mu Ci, i.v.), which circulated for 90 min. The specific bindi ngs in vitro of the 5-HT uptake site ligand [H-3]citalopram and the DA uptake site ligand [I-125]RTI-55 were measured in cryostat sections f rom the prosencephalon. In most structures ipsilateral to the lesion, [H-3]citalopram specific binding was substantially reduced (50-90%). I n the lateral habenula specific binding declined by only 30-40%, refle cting the presence of a 5-HT pathway deviating from the MFB at the mes encephalic flexure. [I-125]RTI-55 binding in the basal ganglia was red uced by 50% on the side of the 5,7-DHT lesion, but was unperturbed in rats pretreated with desmethylimipramine (DMI). 5,7-DHT infusions decr eased the synthesis of [H-3]DA from [H-3]DOPA in vivo in the basal gan glia by (40-90%). Pretreatment with DMI protected [H-3]DA synthesis in the basal ganglia, but not in the olfactory tubercle and amygdala ips ilateral to the lesion. Whereas the 5-HT innervation does not contribu te greatly to [H-3]DA synthesis in the basal ganglia, a substantial pr oportion of [H-3]DA synthesis in olfactory tubercle and amygdala requi res an intact 5-HT innervation.