The PDE4 inhibitor rolipram reverses object memory impairment induced by acute tryptophan depletion in the rat

RATIONALE: The selective type IV phosphodiesterase inhibitor, rolipram, has been shown to improve long-term memory and can reverse the cholinergic deficit caused by scopolamine. However, the underlying mechanisms of action of rolipram remain obscure. OBJECTIVES: The present study investigates the effect of rolipram in a serotonergic-deficit model of acute tryptophan depletion (ATD). In addition, the levels of plasma tryptophan (TRP) were compared to object recognition performance. MATERIALS AND METHODS: The experiments were conducted using male Wistar rats. The time-dependent effect of ATD treatment (a gelatin-based protein mixture) on plasma TRP levels (0, 1, 3, and 6 h after injection) and object recognition task (ORT) performance (0.5, 1, 3, and 6 h after ATD treatment) was examined. The effect of rolipram (0, 0.01, 0.03, and 0.1 mg/kg, i.p.) was tested in the condition in which ATD induced a clear memory deficit. RESULTS: ATD significantly lowered the plasma TRP ratio (TRP/Σlarge neutral amino acid) with a maximum of 48%, approximately 1 h after administration. Furthermore, ATD impairs ORT performance when administered 3 h before testing. Rolipram (0.1 mg/kg) reversed the memory deficit induced by ATD in a dose-dependent manner. CONCLUSIONS: On the basis of previous studies and the ability to reverse a serotonergic deficit, we suggest that rolipram may act through elevation of cyclic adenosine monophosphate levels and subsequent increase in neurotransmitter release.