Inhibition of nitric oxide synthase impairs early olfactory associative learning in newborn rats

The present experiments examined the role of nitric oxide ( NO) in early associative olfactory learning in rats. A preference for peppermint odor was induced by pairing peppermint odor with tactile stimulation in Wistar rat pups, in either a repetitive training paradigm or in a one-trial olfactory learning paradigm. In a first experiment we studied the effect of nitric oxide synthase (NOs) inhibition on early olfactory learning in a repetitive paradigm, by systemic daily injections of NG-nitro-l-arginine methyl ester (l-NAME, 50 mg/kg, i.p.). In order to exclude possible deleterous effects of repeated injections of l-NAME, we explored in a second experiment the effect of a single inhibitor injection in a one-trial olfactory learning paradigm. Inhibition of NOs was performed by either administration of l-NAME (50 mg/kg, i.p.), or 7-nitroindazole (7-NI, 30 mg/kg, i.p.), a more selective inhibitor of the neuronal NOs. We showed that both l-NAME and 7-NI impaired early olfactory associative learning when given before training but not before subsequent testing. Considering that NOs neurons are already widespread in the central nervous system (the olfactory bulb included) during the first postnatal week, the sites where NO inhibition may have acted to impair olfactory learning are discussed. The mechanisms of action of NO in relation with other neurotransmitters known to be necessary for olfactory conditioning in rat pups remain to be established. Impairment by NO synthesis inhibition of the acquisition during the first postnatal week of an olfactory conditioning, but not its recall, suggests a role for NO at synapses involved in that learning.