Distribution and kinetics of galanin infused into the ventral hippocampus of the rat: relationship to spatial learning.

A recent study has shown that ventral hippocampal galanin plays a role in spatial learning and that it has an inhibitory effect on basal acetylcholine release [Ogren S. O. et al. (1996) Neuroscience 75, 1127-1140]. The present studies were designed to compare the in vivo tissue distribution and kinetics of infused galanin (porcine) with the temporal effect of galanin on spatial learning in the rat. Daily bilateral microinfusions of galanin (1.5 nmol/side for five days) via chronic cannulae placed in the ventral hippocampus produced a significant impairment of acquisition of the spatial task when infused 20 min, but not 5 or 60 min, before the daily training session. No overall impairment of memory retention (examined 24 h after the last training session) was observed in the galanin-treated rats. These results indicate that galanin given in the ventral hippocampus produces a time-dependent effect on acquisition. Using an antibody to porcine galanin and immunohistochemistry, galanin infused in the ventral hippocampus was found to be distributed mainly within the ventral part of the hippocampus and around the infusion site. The infused galanin was rapidly cleared from the extracellular space between 5 and 20 min after infusion. Five minutes after infusion of galanin, a number of cells in the ventral hippocampus, both within and outside the zone of extracellularly located galanin, showed a positive galanin-like immunoreactivity. These cells appear morphologically to be medium-sized neurons with a similar position as cells showing neuropeptide Y-like immunoreactivity. At 20 and 60 min after infusion of galanin, no cells with detectable levels of galanin-like immunoreactivity could be seen. These results indicate that the temporal kinetics and distribution of infused galanin are of major importance for its behavioural effect in the ventral hippocampus. The rapid clearance of the infused galanin and its internalization by neuronal endocytotic mechanisms may be important for its effect on cognition.