title: 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.) produced locomotor hyperactivity, disruption of PPI and a number of behaviors indicative of 5-HT activation such as wet-dog shakes, back muscle contractions and forepaw treading. These various behavioral effects of LSD were studied in both Sprague-Dawley and Wistar rats, although with the exception of back muscle contractions which were more prominent in Sprague-Dawley rats, no major strain differences were detected. The PPI disruption induced by LSD (0.1 mg/kg) in Sprague-Dawley rats was completely reversed by pretreatment with the selective 5-HT(2A) antagonist MDL 100907 (0.5 and 1 mg/kg, s.c.). In contrast, pretreatment with antagonists at 5-HT(2C), (SB 242084 (0.5 mg/kg, i.p.)); 5-HT(2B/2C) (SDZ SER 082 (1 mg/kg, s.c.)); 5-HT(1A), ((+)-WAY 100135 (1 and 20 mg/kg, s.c.)) and 5-HT(6) receptors, (RO 04-6790 (30 mg/kg, i.p.)), all failed to influence LSD-induced disruption of PPI. The dopamine DA(2like) receptor antagonist, haloperidol (0.1 and 0.2 mg/kg, s.c.), was without effect against an LSD-induced disruption of PPI. Finally, selective blockade of 5-HT(2A) but not 5-HT(2C) receptors completely abolished the locomotor hyperactivity induced by LSD. These findings provide empirical evidence to support the view that the hallucinogenic effects of LSD are mediated by a direct agonist effect at 5-HT(2A) receptors.
authors.affiliation: Pharmaceuticals Division, Preclinical Studies, F. Hoffmann-La Roche, Basel, Switzerland. abdel@igbmc.u-strasbg.fr
authors.forename: A
authors.initials: A
authors.lastname: Ouagazzal
authors.forename: A J
authors.initials: AJ
authors.lastname: Grottick
authors.forename: J
authors.initials: J
authors.lastname: Moreau
authors.forename: G A
authors.initials: GA
authors.lastname: Higgins
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D018492:Dopamine Antagonists / Q000494:pharmacology; D006213:Hallucinogens / Q000494:pharmacology*; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D013216:Reflex, Startle / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013045:Species Specificity
chemical_list: D018492:Dopamine Antagonists; D006213:Hallucinogens; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D008238:Lysergic Acid Diethylamide