Hippocampal serotonin re-uptake and nocturnal locomotor activity after microinjections of 5,7-DHT in the fornix-fimbria

The role of the hippocampal 5-hydroxytryptamine (5-HT) terminals in the control of locomotor activity was investigated by lesioning 5-HT axons in the fimbria with 5,7-dihydroxytryptamine (5,7-DHT). Rats pretreated with desimipramine (10 mg/kg, i.p.) received microinjections of 5,7-DHT (0, 1, 3, 5 or 10 μg in 0.4 μl ascorbic Ringer's solution) into the fornix-fimbria. On the fourteenth to twenty-first nights after operation, nocturnal locomotor activity was measured in photocell cages. Twenty-eight to thirty days after operation degeneration of 5-HT terminals was assessed by measuring in vitro [³H]5-HT re-uptake in slices of dorsal hippocampus, ventral hippocampus and the septum. Groups injected with 5,7-DHT showed hyperactivity in the night period and increased decrements of activity between tests, both of which were related to the dose of neurotoxin. A reduction of [³H]5-HT re-uptake was found in dorsal hippocampus which was related to the dose of 5,7-DHT, but ventral hippocampal and septal [³H]5-HT re-uptake were not systematically reduced. For each rat, levels of dorsal and ventral hippocampal [³H]5-HT re-uptake were negatively correlated with the mean nocturnal activity from the 7 nights of testing. Levels of dorsal, but not ventral hippocampal [³H]5-HT re-uptake were negatively correlated with the mean nightly decrement of activity. No correlations were found between septal [³H]5-HT and these activity measures. These results, indicate that the increase in nocturnal locomotor activity caused by generalized depletion of 5-HT in the brain may be due to disruption of hippocampal 5-HT terminals supplied by the fornix-fimbria.