Type 4 phosphodiesterase inhibition impairs detection of low odor concentrations in mice

The cAMP-specific phosphodiesterase PDE4A is abundant in the dendrites, soma and axons of olfactory receptor neurons of the mouse, but it is not present in the cilia, where olfactory transduction initiates. Although the function of PDE4A in mammalian olfaction is unknown, patch clamp studies on deciliated olfactory receptor cells in the newt have shown that adrenaline or cAMP analogs can increase the contrast sensitivity to current injection. We used mice to ask whether increasing the levels of cAMP in sensory neurons by inhibiting PDE4A activity with rolipram could lead to changes in the perception of odorants that correspond to the in vitro cellular responses seen in newts. In an automated olfactometer, rolipram treatment (1mg/kg, i.p.) significantly impaired the detection accuracy of 1-propanol at relatively high dilutions but did not affect detection at lower dilutions. Meanwhile, the ability to discriminate amyl acetate alone from a mixture of amyl acetate+citronellal was not affected by rolipram at any odor dilution. In a different task in which mice were trained to discriminate between cups of scented versus unscented sand, rolipram treatment resulted in poorer discrimination at high and better discrimination at low, odor dilutions. In sum, PDE4 inhibition resulted in a consistent decrement in the ability of mice to detect low concentrations of odorants, but the effects of rolipram on detection of higher concentrations were task-dependent.