Potentiation and prolongation of long-term odor memory in neonate rats using a phosphodiesterase inhibitor.
Cyclic AMP has been shown to have a critical role in learning and memory in invertebrates. Here we use the rat pup odor preference learning model in which odor acts as a conditioned stimulus and beta-adrenoceptor stimulation acts as an unconditioned stimulus to test the role of cyclic AMP in an associative mammalian paradigm. A phosphodiesterase inhibitor that prevents cyclic AMP breakdown (cilomilast) makes a low, learning-ineffective dose of a beta-adrenoceptor agonist (isoproterenol, 1mg/kg) an effective unconditioned stimulus in pup odor preference learning. A dose of the phosphodiesterase inhibitor (cilomilast, 1 mg/kg) that induces learning with a weak unconditioned stimulus interferes with learning using a normally optimal unconditioned stimulus (isoproterenol, 2 mg/kg). Cilomilast (3 mg/kg) paired with peppermint odor during learning, prolonged memory at least four times longer than without the drug (24 h vs. 96 h). These data demonstrate a causal role for cyclic AMP in the acquisition and duration of odor preference learning in the rat pup.
McLean
J H
JH
Division of Basic Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada A1B 3V6. mclean@mun.ca
Darby-King
A
A
Harley
C W
CW
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects; D002264:Carboxylic Acids / Q000494:pharmacology; D003214:Conditioning, Classical / Q000187:drug effects*; D003509:Cyclohexanecarboxylic Acids; D004193:Discrimination Learning / Q000187:drug effects; D004347:Drug Interactions; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects*; D009570:Nitriles / Q000494:pharmacology*; D009812:Odorants; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020889:Rolipram / Q000494:pharmacology*; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D002264:Carboxylic Acids; D003509:Cyclohexanecarboxylic Acids; D009570:Nitriles; D010726:Phosphodiesterase Inhibitors; C433247:Cilomilast; D020889:Rolipram; D007545:Isoproterenol