Mescaline: excitatory effects on acoustic startle are blocked by serotonin2 antagonists

The ability of serotonin2 (5-HT2) antagonists to block the excitatory effects of mescaline on the acoustic startle reflex were analyzed. Mescaline (20 mg/kg) caused a consistent increase in the amplitude of the acoustic startle reflex. This effect was blocked in a dose-related fashion by the 5-HT2 antagonist ritanserin (ED50 dose = 0.25 mg/kg IP). In contrast, even a high dose of ritanserin (2.0 mg/kg) did not block the excitatory effects of amphetamine on startle. Other 5-HT2 antagonists (ketanserin, cinanserin, LY 53857) also blocked mescaline's effect, whereas the 5-HT1 antagonist pindolol (5 mg/kg) did not. These results support the hypothesis that the behavioral effects of hallucinogens are mediated by agonist actions at 5-HT2 receptors.