The stimulus properties of LSD in C57BL/6 mice.
BACKGROUND
Drug-induced stimulus control has proven to be a powerful tool for the assessment of a wide range of psychoactive drugs. Although a variety of species has been employed, the majority of studies have been in the rat. However, with the development of techniques which permit the genetic modification of mice, the latter species has taken on new importance. Lysergic acid diethylamide [LSD], the prototypic indoleamine hallucinogen, has not previously been trained as a discriminative stimulus in mice.


OBJECTIVE
To demonstrate the feasibility of LSD-induced stimulus control in the mouse and to provide a preliminary characterization of the stimulus properties of LSD in that species.


METHODS
Male C57BL/6 mice were trained using a left or right nose-poke operant on a fixed ratio 10, water reinforced task following the injection of lysergic acid diethylamide [LSD, 0.17 or 0.30 mg/kg, s.c.; 15 min pretreatment] or vehicle.


RESULTS
Stimulus control was established in 6 of 16 mice at a dose of LSD of 0.17 mg/kg after 39 sessions. An increase in dose to 0.30 mg/kg for the remaining mice resulted in stimulus control in an additional 5 subjects. In the low dose group, subsequent experiments demonstrated an orderly dose-effect relationship for LSD and a rapid offset of drug action with an absence of LSD effects 60 min after injection. When LSD [0.17 mg/kg] was administered in combination with the selective 5-HT2A antagonist, M100907, LSD-appropriate responding was significantly but incompletely reduced to approximately 50%; concurrently, response rates declined significantly. In mice trained with a dose of LSD of 0.30 mg/kg, full generalization to the phenethylamine hallucinogen, [-]-2,5-dimethoxy-4-methylamphetamine [DOM] was observed.


CONCLUSIONS
The present data demonstrate the feasibility of LSD-induced stimulus control in the mouse. The general features of stimulus control by LSD in the mouse closely resemble those observed in the rat but the present data suggest that there may be significant differences as well.
Winter
J C
JC
Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, 102 Farber Hall, Buffalo, NY 14214-3000, USA. jcwinter@buffalo.edu
Kieres
A K
AK
Zimmerman
M D
MD
Reissig
C J
CJ
Eckler
J R
JR
Ullrich
T
T
Rice
K C
KC
Rabin
R A
RA
Richards
J B
JB
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004192:Discrimination, Psychological / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005464:Fluorobenzenes / Q000494:pharmacology; D006213:Hallucinogens / Q000494:pharmacology; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D012702:Serotonin Antagonists / Q000494:pharmacology; D013997:Time Factors
D005464:Fluorobenzenes; D006213:Hallucinogens; D010880:Piperidines; D012702:Serotonin Antagonists; D008238:Lysergic Acid Diethylamide; C079049:volinanserin