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Here we applied behavioral testing, pharmacology, and in vivo electrophysiology to determine the function of the serotonin 5-HT_5A receptor in goldfish startle plasticity and sensorimotor gating. In an initial series of behavioral experiments, we characterized the effects of a selective 5-HT_5A antagonist, SB-699551 (3-cyclopentyl-N-[2-(dimethylamino)ethyl]-N-[(4′-{[(2-phenylethyl)amino]methyl}-4-biphenylyl)methyl]propanamide dihydrochloride), on prepulse inhibition of the acoustic startle response. Those experiments showed a dose-dependent decline in startle rates in prepulse conditions. Subsequent behavioral experiments showed that SB-699551 also reduced baseline startle rates (i.e., without prepulse). To determine the cellular mechanisms underlying these behaviors, we tested the effects of two distinct selective 5-HT_5A antagonists, SB-699551 and A-843277 (N-(2,6-dimethoxybenzyl)-N′[4-(4-fluorophenyl …