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), wh ereas 5-HT facilitates noradrenergic actions. In this study, we examined th e phosphorylation of an important transcription factor, cAMP response eleme nt binding protein (CREB), which has been implicated in long-term-memory fo rmation (McLean et al. 1999) during NE-induced odor preference learning in normal and olfactory bulb 5-HT-depleted rat pups. We also examined NE modul ation of olfactory nerve-evoked field potentials (ON-EFPs) in anesthetized normal and bulbar 5-HT depleted pups. Systemic injection of 2 mg/kg isoprot erenol (beta -adrenoceptor agonist) induced odor preference learning, enhan ced pCREB expression in the olfactory bulbs at 10 min after odor pairing, a nd 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, enhan ced phosphorylated CREB (pCREB) expression, and increased ON-EFPs in bulbar 5-HT-depleted pups. These outcomes suggest that NE and 5-HT promote specif ic biochemical and electrophysiological changes that may critically underli e odor preference learning.