Habituation of tactile startle is altered by drugs acting on serotonin-2 receptors.

Ligand binding studies indicate that multiple serotonin (5-HT) binding sites exist in the brain. To relate these putative receptor subtypes to startle reactivity and habituation, compounds with varying specificities for 5iHT1 and 5-HT2 binding sites were administered to rats prior to the presentation of 201 startling tactile stimuli. The 5-HT2 antagonists cyproheptadine, cinanserin, ritanserin, and ketanserin increased the rate of tactile startle habituation without affecting initial levels of reactivity. The 5-HT1A agonists 8-hydroxy-2-(di-n-propylamino)tetralin, ipsapirone, and 5-methoxy-N,N-dimethyltryptamine, the 5-HT1B agonist m-trifluoromethylphenylpiperazine, and the 5-HT2 agonist quipazine affected startle reactivity rather than having specific effects on habituation. The effects of the exogenous 5-HT2 antagonists were consistent with the effects of manipulations of endogenous 5-HT. Specifically, the serotonin depleting agents parachlorophenylalanine and parachloroamphetamine accelerated startle habituation. Conversely, the serotonin reuptake inhibitor fluoxetine decreased startle habituation. These findings support the hypothesis that serotonergic systems modulate the habituation of tactile startle via actions at 5-HT2 receptors.