INDUCTION AND MAINTENANCE OF GANGLIONIC LONG-TERM POTENTIATION REQUIRE ACTIVATION OF 5-HYDROXYTRYPTAMINE (5-HT3) RECEPTORS

1. An extracellular recording technique was used to study the effects of 5-hydroxytryptamine (5-HT, serotonin) on the tetanus-induced long-g erm potentiation (LTP) of the nicotinic pathway of transmission in the superior cervical ganglion (SCG) of the rat. The postganglionic compo und action potential (CAP), made submaximal by treatment with hexameth onium (0.4 mM), was used as an index of transmission in the ganglion. 2. Serotonin (10 mu M) markedly enhanced the magnitude of LTP without affecting the post-tetanic potentiation (PTP). The serotonin (2-30 mu M) concentration-response curve for LTP was bell shaped as no enhancem ent was seen with 30 mu M serotonin. This may largely be due to activa tion of a 5-HT1 receptor subtype and not to desensitization. 3. When s uperfused before tetanus, the 5-HT1A receptor agonist 8-hydroxydipropy laminotetralin (8-OH-DPAT, 5 mu M) prevented the expression of LTP wit hout affecting PTP. 4. Pretreatment of ganglia with the 5-HT2 receptor agonist R-(+)-dimethoxy-4-iodoamphetamine (R-(+)-DOI, 1 mu) enhanced the tetanus-induced LTP. Similar treatment with the 5-HT2 receptor ant agonist ketanserin (3 mu M) had no significant effect on LTP. 5. Pretr eatment of ganglia with the 5-HT3 receptor agonist 1-m-(chlorophenyl)b iguanide (m-CPBG, 1 mu M), markedly increased (300%) the tetanus-induc ed LTP. Similar pretreatment with the 5-HT3 receptor antagonist 3-trop anyl-3,5-dichlorobenzoate (MDL 72222, 0.5 mu M) completely prevented t he expression of LTP. Fully expressed LTP was reversibly blocked by MD L 72222 when applied during the maintenance phase of LTP. 6. Tetanic s timulation of monoamine-depleted ganglia (from reserpine-pretreated ra ts, 3 mg kg(-1) for 24 h) failed to induce LTP. 7. In monoamine-deplet ed ganglia, tetanus preceded by superfusion with m-CPBG readily induce d LTP. MDL 72222 completely blocked this LTP. However, in these gangli a tetanus failed to induced LTP when m-CPBG was given 2 min (during PT P) or 1 h after tetanus. 8. Tetanic stimulation of monoamine-depleted ganglia in the presence of R-(+)-DOI failed to induced LTP. 9. We conc lude that tetanus-induced LTP of the SCG of the rat requires activatio n of 5-HT3 receptors both for induction and maintenance.