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


OBJECTIVE
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.


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/Sigmalarge 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.
Rutten
K
K
Department of Psychiatry and Neuropsychology, Brain and Behavior Institute, Maastricht University, Universiteitssingel 50, 6200 MD, Maastricht, The Netherlands. k.rutten@np.unimaas.nl
Lieben
C
C
Smits
L
L
Blokland
A
A
D000596:Amino Acids / Q000097:blood / Q000172:deficiency; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D045424:Complex Mixtures / Q000008:administration & dosage; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005780:Gelatin / Q000008:administration & dosage; D007274:Injections, Intraperitoneal; D008297:Male; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders / Q000188:drug therapy*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D020889:Rolipram / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism; D014364:Tryptophan / Q000097:blood / Q000172:deficiency
D000596:Amino Acids; D045424:Complex Mixtures; D010726:Phosphodiesterase Inhibitors; D012701:Serotonin; D014364:Tryptophan; D005780:Gelatin; D000242:Cyclic AMP; D020889:Rolipram