In male Sprague-Dawley rats, hallucinogens and other psychoactive drugs were tested for their effects on the tactile startle response to air-puff stimuli. Phenylethylamine-derived compounds such as mescaline increased startle magnitudes throughout the session, suggesting increased reactivity. Indoleamine hallucinogens like LSD did not increase startle responding. LSD did increase the response to the first stimulus with more intense air-puffs and impaired habituation when the number of stimuli increased: control rats' responses decreased by 70% across the session, while LSD-treated rats' responses decreased by only 32%. These results suggest that LSD and phenylethylamine-derived hallucinogens differ in their effects on tactile startle.
Electrolytic lesions targeting either the dorsal or median raphe nucleus in rats were used to test whether serotonin-containing midbrain cells mediate the effects of mescaline on startle responses. Lesion effectiveness was confirmed by decreased tryptophan hydroxylase activity in the striatum or hippocampus. Median, but not dorsal, raphe lesions increased startle magnitudes to air-puff stimuli. Despite baseline differences, mescaline (10 mg/kg) produced comparable 25% increases in startle magnitudes in both sham- and raphe-lesioned animals. This result does not support the hypothesis that mescaline's effect on startle is mediated by the midbrain raphe nuclei.