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

Abstract

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.

Mescaline effects on rat behavior and its time profile in serum and brain tissue after a single subcutaneous dose

“…Unlike others who have reported an increase in startle reaction (Davis 1987;Geyer et al 1978), we observed a decrease in startle produced by mescaline 100 mg/kg at 60 min post-treatment. This could reflect the robust motor changes produced by the drug.…”

“…On the other hand, a 0-to 20-min pretest interval after either i.p. or s.c. administration was used by others in various tests, e.g., Wing et al (1990); Sykes (1986); Harris et al (1978); Gorelick and Bridger (1977); Davis (1987); Geyer et al (1979); Silva and Calil (1975). Interestingly, in previously published drug discrimination studies, animals were able to discriminate mescaline 5 and 15 min after relatively low doses of mescaline (9.9 and 15 mg/kg; Browne et al 1974;Hirschhorn and Winter 1971).…”

“…However, animal data from mescaline are much less consistent, and the majority of it was published more than 20 years ago. Davis (1987) has studied the effect of mescaline on acoustic startle resulting in an increase of startle reaction induced by 20 mg/kg (Davis 1987). Mescaline also increased tactile startle response magnitudes in experiments done by Geyer et al (1978).…”

Serotonergic hallucinogens as translational models relevant to schizophrenia

“…Importantly, acute administration of LSD to rats reduced habituation of tactile startle provoked by air-puffs (Figure 2) (Geyer et al, 1978; Geyer and Braff, 1987), an effect that is lost when LSD is administered chronically (Braff and Geyer, 1980). Mescaline also attenuates habituation of acoustic startle in rats (Davis, 1987), and this effect is blocked by the 5-HT 2A/2C antagonists ritanserin, ketanserin, LY 53857, and cinanserin. Psilocybin, however, did not have significant effects on startle reactivity or habituation when tested in human subjects (Gouzoulis-Mayfrank et al, 1998c; Vollenweider et al, 2007; Quednow et al, 2012).…”

Animal Models for Anxiety and Response to Serotonergic Drugs

“…Because the 5-HT2 receptor also mediates hallucinations, 5-HT2 receptor agonists are not suitable for inferences about the role of 5-HT2 receptors in anxiety models [34], Among the antagonists, there are useful tools to study the role of 5-HT2 receptors. There quency or the monophasic square-wave pulses was adjusted after each trial (1 trial/min) to titrate to the effective frequency for escape.…”