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Selective remodeling of rabbit frontal cortex: relationship between 5-HT2A receptor density and associative learning
Journal article   Peer reviewed

Selective remodeling of rabbit frontal cortex: relationship between 5-HT2A receptor density and associative learning

John A Harvey, Jennifer L Quinn, Reijun Liu, Vincent J Aloyo and Anthony G Romano
Psychopharmacology, v 172(4), pp 435-442
Apr 2004
DOI: https://doi.org/10.1007/s00213-003-1687-4
PMID: 14685644
Featured in Collection :   UN Sustainable Development Goals @ Drexel

Abstract

Rabbits Lysergic Acid Diethylamide - analogs & derivatives Blinking - drug effects Conditioning, Classical - drug effects Learning - drug effects Male Learning - physiology Animals Prefrontal Cortex - drug effects Piperidines - pharmacology Time Factors Lysergic Acid Diethylamide - pharmacology Prefrontal Cortex - metabolism Behavior, Animal - drug effects Ligands Serotonin 5-HT2 Receptor Agonists Receptor, Serotonin, 5-HT2A - metabolism Prefrontal Cortex - physiology
Associative learning during classical trace eyeblink conditioning has been shown to be regulated by serotonin 5-HT(2A )receptors and to be critically dependent on the integrity of frontal cortex. Chronic administration of 5-HT(2A) ligands has been shown to produce a selective up- or down-regulation of 5-HT(2A) receptors in frontal cortex. We examined whether alterations in 5-HT(2A) receptor density had a functional significance with respect to associative learning. Animals received chronic injections of LSD, BOL or MDL11,939 and 1 day later began classical trace conditioning of the eyeblink response. The density of 5-HT(2A) receptors in frontal cortex was significantly increased at 1-4 days after the cessation of chronic injections of the selective 5-HT(2A) receptor ligand MDL11,939. Rabbits demonstrated an enhancement of associative learning when training began at 1 day after cessation of chronic MDL11,939 injections, but acquired at the same rate as controls when training began at 8 days after cessation of injections, a time when receptor density had returned to control levels. Animals that began training 1 day after chronic injections of BOL or LSD, drugs that produce decreases in 5-HT(2A) receptor density, demonstrated normal rates of acquisition. These results indicate that increases in the density of 5-HT(2A) receptors in frontal cortex are associated with increases in the rate of associative learning, and further support an important role for this receptor in cortical circuitry that mediates learning. More generally, these results suggest an approach for functional remodeling of brain regions in the adult animal.

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Web of Science research areas
Neurosciences
Pharmacology & Pharmacy
Psychiatry
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