Noradrenergic modulation of pheromone-induced odor learning and brain activation in newborn rabbits

Learning maternal odors is crucial for mammalian newborns, who must locate the mother's nipples to survive. In the newborn rabbit, the mammary pheromone (MP) present in the milk not only allows the pups to locate the nipples, but also promotes associative memory of neutral odorants. The noradrenergic system modulates neonatal learning in humans and rodents, but its role in newborn rabbits has never been investigated. Intraperitoneal injection of propranolol, a β-adrenoceptors antagonist, blocked acquisition, but not memory consolidation or retrieval, of MP-induced odor memory. Moreover, gene expression analyses revealed that propranolol attenuated c-Fos neuronal activation induced by odor learning in the olfactory bulb and to a lesser extent in the anterior piriform cortex, but not in the hippocampus, of rabbit pups. Interestingly, propranolol had no effect on c-Fos activation induced by MP alone indicating a specific effect of propranolol on neuronal activation induced by associative learning. These effects were not associated with a change in β-adrenoceptors expression in these brain areas. This highlights the crucial role of noradrenergic system in neonatal odor learning in mammals and suggest that the MP promotes odor learning by activating β-adrenoceptors in olfactory brain areas in rabbit pups. This pheromone-induced memory provides a great opportunity to explore the neurobiology of neonatal learning.