Evidence for a dopaminergic innervation of the cat lateral habenula: its role in controlling serotonin transmission in the basal ganglia.

The presence of a dopaminergic innervation of the cat lateral habenula and its possible role in modulating serotonin transmission within the basal ganglia were investigated using both in vitro and in vivo approaches. A high density of [3H]spiroperidol binding sites with similar affinities for domperidone and apomorphine as those present in the cat striatum were found in the habenula. By means of the push-pull cannula technique, a substantial release of [3H]dopamine continuously formed from [3H]tyrosine was detected in the lateral habenula of halothane-anesthetized cats since the amount of [3H]catecholamines was enhanced in the presence of benztropine, an inhibitor of dopamine uptake into dopaminergic nerve terminals. Furthermore, in anesthetized animals with a push-pull cannula implanted in each caudate nucleus and substantia nigra habenular applications of dopamine (10(-7) M) reduced nigral but not striatal release of [3H]serotonin continuously formed from [3H]tryptophan. This change was prevented either by the delivery of domperidone to the lateral habenula or by the blockade of GABAergic transmission (picrotoxin 10(-5) M) in the dorsal raphe. These data support the involvement of habenulo-raphe pathways in the regulation of serotonin transmission in the cat basal ganglia and indicate that dopaminergic inputs to the lateral habenula participate in such a control.