Effect of LSD on Prepulse Inhibition and Spontaneous Behavior in the Rat A Pharmacological Analysis and Comparison between Two Rat Strains

Abstract

The goal of the present study was to better delineate the mechanisms of action of the prototypical hallucinogen LSD. LSD (0.03, 0.1 and 0.3 mg/kg, s.c.) Delineation of the neurobiological mechanisms underlying the profound effects of hallucinogens on perception, mood, and thought processes has been the subject of great interest over the years. There is now increasing evidence that the two major classes of hallucinogens, the indolamines (e.g., LSD) and the phenethylamines (e.g., DOM and DOI) share a common site of action at 5-HT 2 receptor populations (Barnes and Sharp 1999;Aghajanian and Marek 2000). 5-HT 2 receptors consist of three distinct subtypes, namely 5-HT 2A , 5-HT 2B and 5-HT 2C (for review see Barnes and Sharp 1999). They are G-protein-coupled receptors and share a high degree of homology in their amino acid sequences. Binding and cellular studies have shown that LSD, DOI, DOM and other related hallucinogens share a high affinity for the 5-HT 2A/B/C receptor subtypes (Egan et al. 1998;Nelson et al. 1999;Porter et al. 1999).

Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects

“…Thus, the effects of LSD and psilocybin on the acoustic startle response and its modulation were quite similar. Additionally, the disruption of PPI induced by psilocybin in humans at a short ISI (30ms) was prevented by administration of a 5-HT 2A receptor antagonist (69), consistent with similar preclinical studies of LSD (41). In contrast to the findings with LSD and psilocybin, DMT or ayahuasca had no Schmid et al Effects of LSD 13 effects on PPI, startle reactivity, or habituation in humans (19,70).…”

“…Specifically, prepulse inhibition (PPI) of the acoustic startle Schmid et al Effects of LSD 4 response serves as an operational measure of sensorimotor gating that can be assessed in animals and humans (35). PPI is impaired in schizophrenia and also in prodromal states and early phases (35)(36)(37)(38), and hallucinogens like LSD acutely disrupt PPI in animals (39)(40)(41)(42)(43)(44).…”

Psychedelics

“…Similarly, Ouagazzal et al (2001) demonstrated that the decrease in PPI induced by LSD in rats also was mediated by 5-HT 2A receptors. The disruption of PPI induced by LSD in Sprague-Dawley rats was completely blocked by pretreatment with the highly selective 5-HT 2A antagonist M100907.…”

Animal Models of Serotonergic Psychedelics

“…86 In humans, psilocybin disrupts PPI at short interstimulus intervals (ISIs), but has no effect at medium ISIs, and, notably, enhances PPI at long ISIs. 87,88 In rodents, some, but not all, of these studies suggest that psychedelics disrupt PPI at short, medium and long ISIs. 89−91 It is also worth noting that, while both lisuride and LSD disrupt PPI in rats, pretreatment with the 5-HT 2A antagonist α-phenyl-1-(2-phenylethyl)-4-piperidinemethanol (MDL11939) reverses the effect of LSD, but not that of lisuride.…”