Lesioning and recovery of the serotoninergic projections to the hippocampus

The time course of the changes of the hippocampal 5-hydroxytryptamine (5-HT) system after a lesion of the dorsal afferents to this brain area was studied by measuring the content of 5-HT and of 5-hydroxyindoleacetic acid (5-HIAA) in the dorsal, medial and ventral hippocampus. Furthermore, the binding sites for [³H]5-HT, [³H]ketanserin,[³H]imipramine and [³H]mianserin and a 5-HT-mediated behavior (head-twitch responses) were studied in controls and in animals bearing such a lesion. The contents of 5-HT and of 5-HIAA are higher in the ventral than in the dorsal hippocampus. Seven days after the lesion the 5-HT content decreases by 78% in the dorsal and by 50% in the ventral hippocampus. However, 60 days later, a partial recovery, possibly due to a collateral sprouting, does occur. The ratios between 5-HIAA and 5-HT are also increased 10, 14 and 21 days after the lesion, suggesting an increased utilization of the amine by the remaining neuronal terminals. The B_max of the recognition sites for [³H]5-HT and [³H]mianserin, but not those for [³H]ketanserin are increased 10 days after the lesion and this increase lasts at least 30 days. Finally, starting 10 days after surgery and lasting for 40 days, a 5-HT-mediated behavior (head-twitch responses) shows supersensitivity. These results suggest that important changes occur in the 5-HT innervation of the hippocampus after a mechanical lesion: among these we showed a slow collateral sprouting, an increased utilization of the amine and a supersensitivity of 5-HT receptors.