Intrahippocampal LSD accelerates learning and desensitizes the 5-HT(2A) receptor in the rabbit, Romano et al.
BACKGROUND
Parenteral injections of d-lysergic acid diethylamide (LSD), a serotonin 5-HT(2A) receptor agonist, enhance eyeblink conditioning. Another hallucinogen, (±)-1(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), was shown to elicit a 5-HT(2A)-mediated behavior (head bobs) after injection into the hippocampus, a structure known to mediate trace eyeblink conditioning.


OBJECTIVE
This study aims to determine if parenteral injections of the hallucinogens LSD, d,l-2,5-dimethoxy-4-methylamphetamine, and 5-methoxy-dimethyltryptamine elicit the 5-HT(2A)-mediated behavior of head bobs and whether intrahippocampal injections of LSD would produce head bobs and enhance trace eyeblink conditioning.


METHODS
LSD was infused into the dorsal hippocampus just prior to each of eight conditioning sessions. One day after the last infusion of LSD, DOI was infused into the hippocampus to determine whether there had been a desensitization of the 5-HT(2A) receptor as measured by a decrease in DOI-elicited head bobs.


RESULTS
Acute parenteral or intrahippocampal LSD elicited a 5-HT(2A) but not a 5-HT(2C)-mediated behavior, and chronic administration enhanced conditioned responding relative to vehicle controls. Rabbits that had been chronically infused with 3 or 10 nmol per side of LSD during Pavlovian conditioning and then infused with DOI demonstrated a smaller increase in head bobs relative to controls.


CONCLUSIONS
LSD produced its enhancement of Pavlovian conditioning through an effect on 5-HT(2A) receptors located in the dorsal hippocampus. The slight, short-lived enhancement of learning produced by LSD appears to be due to the development of desensitization of the 5-HT(2A) receptor within the hippocampus as a result of repeated administration of its agonist (LSD).
Romano
Anthony G
AG
Department of Pharmacology and Physiology, Drexel University College of Medicine, 245 N. 15th Street, 8th Floor, NCB, Mail stop # 488, Philadelphia, PA 19102, USA. anthony.romano@drexelmed.edu
Quinn
Jennifer L
JL
Li
Luchuan
L
Dave
Kuldip D
KD
Schindler
Emmanuelle A
EA
Aloyo
Vincent J
VJ
Harvey
John A
JA
D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001767:Blinking / Q000187:drug effects; D003214:Conditioning, Classical / Q000187:drug effects; D006213:Hallucinogens / Q000008:administration & dosage / Q000494:pharmacology; D019416:Head Movements / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007267:Injections; D007858:Learning / Q000187:drug effects; D008238:Lysergic Acid Diethylamide / Q000008:administration & dosage / Q000494:pharmacology*; D008732:Methoxydimethyltryptamines / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects* / Q000378:metabolism; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology
D006213:Hallucinogens; D008732:Methoxydimethyltryptamines; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D017366:Serotonin Receptor Agonists; D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine; D008238:Lysergic Acid Diethylamide
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