Isoproterenol increases CREB phosphorylation and olfactory nerve-evoked potentials in normal and 5-HT-depleted olfactory bulbs in rat pups only at doses that produce odor preference learning.
Norepinephrine (NE) and serotonin (5-HT) are important modulators of early odor preference learning. NE can act as an unconditioned stimulus (UCS), whereas 5-HT facilitates noradrenergic actions. In this study, we examined the phosphorylation of an important transcription factor, cAMP response element binding protein (CREB), which has been implicated in long-term-memory formation (McLean et al. 1999) during NE-induced odor preference learning in normal and olfactory bulb 5-HT-depleted rat pups. We also examined NE modulation of olfactory nerve-evoked field potentials (ON-EFPs) in anesthetized normal and bulbar 5-HT depleted pups. Systemic injection of 2 mg/kg isoproterenol (beta-adrenoceptor agonist) induced odor preference learning, enhanced pCREB expression in the olfactory bulbs at 10 min after odor pairing, and increased ON-EFPs in normal rat pups but not in bulbar 5-HT-depleted rat pups. A dose of 6 mg/kg isoproterenol, which was ineffective in modulating these measures in normal rat pups, induced odor preference learning, enhanced phosphorylated CREB (pCREB) expression, and increased ON-EFPs in bulbar 5-HT-depleted pups. These outcomes suggest that NE and 5-HT promote specific biochemical and electrophysiological changes that may critically underlie odor preference learning.
Yuan
Q
Q
Division of Basic Medical Sciences, Memorial University of Newfoundland, St. John's, Newfoundland A1B 3V6, Canada.
Harley
C W
CW
Bruce
J C
JC
Darby-King
A
A
McLean
J H
JH
D000818:Animals; D003213:Conditioning, Psychological; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D005071:Evoked Potentials / Q000187:drug effects* / Q000502:physiology; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology*; D007858:Learning / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009812:Odorants; D009830:Olfactory Bulb / Q000502:physiology*; D009832:Olfactory Nerve / Q000187:drug effects / Q000502:physiology*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000502:physiology*
D017362:Cyclic AMP Response Element-Binding Protein; D012701:Serotonin; D007545:Isoproterenol