The effect of unilateral neurotoxic lesions to serotonin fibres 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 the 5-hydroxytryptamine (5-HT, serotonin) innervation of rat telencephalon to the synthesis of dopamine (DA) from exogenous L-DOPA. One week after stereotaxic infusions of 5,7-dihydroxytryptamine (5,7-DHT, 1.6 mu g) into the right medial forebrain bundle (MFB), rats received [H-3]DOPA (200 mu Ci, i.v.), which circulated for 90 min. The specific bindings 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 from the prosencephalon. In most structures ipsilateral to the lesion, [H-3]citalopram specific binding was substantially reduced (50-90%). In the lateral habenula specific binding declined by only 30-40%, reflecting the presence of a 5-HT pathway deviating from the MFB at the mesencephalic flexure. [I-125]RTI-55 binding in the basal ganglia was reduced by 50% on the side of the 5,7-DHT lesion, but was unperturbed in rats pretreated with desmethylimipramine (DMI). 5,7-DHT infusions decreased the synthesis of [H-3]DA from [H-3]DOPA in vivo in the basal ganglia by (40-90%). Pretreatment with DMI protected [H-3]DA synthesis in the basal ganglia, but not in the olfactory tubercle and amygdala ipsilateral to the lesion. Whereas the 5-HT innervation does not contribute greatly to [H-3]DA synthesis in the basal ganglia, a substantial proportion of [H-3]DA synthesis in olfactory tubercle and amygdala requires an intact 5-HT innervation.