Fluoxetine and 8-OH-DPAT in the lateral septum enhances and impairs retention of an inhibitory avoidance response in rats

The present study investigated the role of lateral septal serotonin (5HT) in memory consolidation and the subtype of 5HT receptors involved in this process. Rats with cannulae implanted bilaterally into the lateral septum were trained in an inhibitory avoidance task. Immediately after training, the septal serotonergic function was manipulated by pharmacological agents selectively blocking 5HT reuptake (fluoxetine and zimelidine), antagonizing 5HT₂ receptors (ketanserin and ritanserin), or activating 5HT_1A receptors, respectively. Results indicated that direct fluoxetine infusions into the lateral septum at a dose of 6 μg/0.5 μl and zimelidine at a dose of 5 μg/0.5 μl both markedly enhanced memory. Intralateral septal injections of ketanserin (0.3 μg/0.5 μl and 0.5 μg/0.5 μl) and ritanserin (0.3 μg/0.5 μl and 0.6 μg/0.5 μl) did not have a significant effect by themselves on memory, and neither did they attenuate the memory-facilitating effect of fluoxetine in the same area. Intralateral septal infusions of 8-hydroxy-2-(di-n-propylamino)tetralin at 5 μg/0.5 μl significantly impaired memory retention. These findings altogether support the notion that the lateral septal nuclei of rats are involved in the memory processes of inhibitory avoidance learning. Furthermore, postsynaptic 5HT receptor activation (not the 5HT₂ receptor subtype) probably exerts a facilitatory effect while presynaptic 5HT_1A receptor activation exerts an impairing effect on the memory consolidation process, probably due to autoreceptor inhibition of 5HT release.