Inhibitory influence via 5-HT3 receptors on the induction of LTP in mossy fiber-CA3 system of guinea-pig hippocampal slices

The effects of 5-HT3-receptor-related agents on long-term potentiation (LTP) in the mossy fiber-CA3 system were studied in guinea pig hippocampal slices. 5-HT3 receptor agonists, 1-(m-chlorophenyl)-biguanide (mCPBG) and 2-methyl serotonin (2-Me-5-HT) significantly attenuated the magnitude of LTP of the population spike at 0.3-1 microM and at 10 microM respectively. At these doses neither of these drugs did affect the amplitude of the population spike (PSA) evoked by test stimuli in the absence of tetanic stimulation. The attenuating effect of mCPBG on LTP was reversed by the GABAA receptor antagonist bicuculline. On the other hand, 5-HT3 receptor antagonists ondansetron and granisetron significantly augmented the magnitude of LTP at 1-3 microM and at 0.1-0.3 microM, respectively, without changes in PSA before tetanus. The augmenting effect of granisetron on LTP was partially but significantly reversed by the muscarinic receptor antagonist atropine. These findings suggest that the induction of the LTP in the mossy fiber-CA3 system is inhibited by an activation of 5-HT3 receptors through the facilitation of GABAergic neurons (GABAA receptors) and the inhibition of cholinergic neurons (muscarinic receptors).