Abstract
5-HT has a powerful modulatory action on the firing properties of single neurons as well as on locomotor activity. In lamprey, 5-HT increases the neuronal firing frequency in spinal neurons by reducing the conductance in Ca 2+-dependent K + channels (K Ca) underlying the slow afterhyperpolarization (sAHP), and it also lowers burst frequency of the spinal locomotor network. To elucidate which type of 5-HT receptor mediates these effects, different specific receptor agonists and antagonists were applied during intracellular current lamp recordings and during NMDA-induced fictive locomotion in the lamprey spinal cord in vitro preparation. The 5-HT 1A receptor agonist 8-OH-DPAT ((±)-8-hydroxy-dipropylaminotetralin hydrobromide), the 5-HT 1 receptor agonist 5-CT (5-car☐yamidotryptamine maleate) and the 5-HT 2 receptor agonist α-CH 3-5-HT (α-methylserotonin maleate) all reproduced the actions of 5-HT at both the cellular and the network levels. The effects of all agonists were completely or partially blocked by the 5-HT 1A and 5-HT 2 receptor antagonist spiperone (spiroperidol hydrochloride) while selective 5-HT 2 receptor antagonists were ineffective. The selective 5-HT 1A receptor antagonist S(−)-UH301 (S(−)-5-fluoro-8-hydroxy-dipropylaminotetralin hydrochloride) also counteracted the effect of 5-HT on the sAHP. 5-HT 3 and 5-HT 4 receptor agonists and antagonists were without effects. The intracellular coupling mechanism was not sensitive to pertussis toxin nor to the cAMP dependent protein kinase blocker (Rp)-cAMPS. These results indicate that the intracellular coupling mechanism is not likely to be due to a down regulation of adenylate cyclase activity or through a direct modulation of K + channels, as is common for 5-HT 1 receptors. The present results taken together with previous data indicates that the receptor responsible for the effects of 5-HT on the sAHP, and on the locomotor pattern generator in lamprey shares certain features, but is not identical to the mammalian 5-HT 1A receptor.
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