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.
Rats given 20–30 μg/kg LSD avoided a novel holeboard chamber during the first half of a 1-hour session, reducing all activity measures such as crossovers, rearings, and hole pokes. In the second half, LSD-treated rats maintained steady responding while controls continued to decline. Despite initial avoidance, LSD-treated rats made consistently longer hole pokes into floor holes and showed more diverse locomotion patterns than controls. Most notably, they failed to develop the stereotyped excursion routes from the home cage to the holeboard that controls established. The authors suggest LSD potentiates both neophobic avoidance and investigatory responses by slowing behavioral habituation.