The effect of unilateral neurotoxic lesions to serotonin fibres in the medial forebrain bundle on the metabolism of [3H]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-dihydroxy-tryptamine (5,7-DHT, 1.6 micrograms) into the right medial forebrain bundle (MFB), rats received [3H]DOPA (200 microCi,i.v.), which circulated for 90 min. The specific bindings in vitro of the 5-HT uptake site ligand [3H]citalopram and the DA uptake site ligand [125I]RTI-55 were measured in cryostat sections from the prosencephalon. In most structures ipsilateral to the lesion, [3H]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. [125I]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 [3H]DA from [3H]DOPA in vivo in the basal ganglia by (40-90%). Pretreatment with DMI protected [3H]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 [3H]DA synthesis in the basal ganglia, a substantial proportion of [3H]DA synthesis in olfactory tubercle and amygdala requires an intact 5-HT innervation.
Cumming
P
P
Montreal Neurological Institute, McGill University, Canada.
Ljubic-Thibal
V
V
Laliberté
C
C
Diksic
M
M
D015116:5,7-Dihydroxytryptamine / Q000633:toxicity*; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D003891:Desipramine / Q000494:pharmacology; D004295:Dihydroxyphenylalanine / Q000008:administration & dosage / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000008:administration & dosage / Q000378:metabolism*; D007150:Immunohistochemistry; D007275:Injections, Intravenous; D008297:Male; D008474:Medial Forebrain Bundle / Q000187:drug effects / Q000502:physiology*; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology*; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D018490:Serotonin Agents / Q000633:toxicity*; D013687:Telencephalon / Q000187:drug effects / Q000378:metabolism*
D018759:Adrenergic Uptake Inhibitors; D015259:Dopamine Agents; D011985:Receptors, Serotonin; D018490:Serotonin Agents; D015116:5,7-Dihydroxytryptamine; D004295:Dihydroxyphenylalanine; D003891:Desipramine; D004298:Dopamine