Characterization of behavioral and endocrine effects of LSD on zebrafish.
Lysergic acid diethylamide (LSD) is a potent hallucinogenic drug that strongly affects animal and human behavior. Although adult zebrafish (Danio rerio) are emerging as a promising neurobehavioral model, the effects of LSD on zebrafish have not been investigated previously. Several behavioral paradigms (the novel tank, observation cylinder, light-dark box, open field, T-maze, social preference and shoaling tests), as well as modern video-tracking tools and whole-body cortisol assay were used to characterize the effects of acute LSD in zebrafish. While lower doses (5-100 microg/L) did not affect zebrafish behavior, 250 microg/L LSD increased top dwelling and reduced freezing in the novel tank and observation cylinder tests, also affecting spatiotemporal patterns of activity (as assessed by 3D reconstruction of zebrafish traces and ethograms). LSD evoked mild thigmotaxis in the open field test, increased light behavior in the light-dark test, reduced the number of arm entries and freezing in the T-maze and social preference test, without affecting social preference. In contrast, LSD affected zebrafish shoaling (increasing the inter-fish distance in a group), and elevated whole-body cortisol levels. Overall, our findings show sensitivity of zebrafish to LSD action, and support the use of zebrafish models to study hallucinogenic drugs of abuse.
Grossman
Leah
L
Department of Pharmacology, Neuroscience Program and Zebrafish Neuroscience Research Consortium (ZNRC), Tulane University Medical School, 1430 Tulane Ave., New Orleans, LA 70112, USA.
Utterback
Eli
E
Stewart
Adam
A
Gaikwad
Siddharth
S
Chung
Kyung Min
KM
Suciu
Christopher
C
Wong
Keith
K
Elegante
Marco
M
Elkhayat
Salem
S
Tan
Julia
J
Gilder
Thomas
T
Wu
Nadine
N
Dileo
John
J
Cachat
Jonathan
J
Kalueff
Allan V
AV
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001826:Body Fluids / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D005260:Female; D006213:Hallucinogens / Q000494:pharmacology*; D006854:Hydrocortisone / Q000032:analysis; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology*; D008297:Male; D014741:Video Recording / Q000379:methods; D015027:Zebrafish
D006213:Hallucinogens; D008238:Lysergic Acid Diethylamide; D006854:Hydrocortisone