Phosphodiesterase type 1 inhibition improves learning in rats exposed to alcohol during the third trimester equivalent of human gestation.
Deficits in learning and memory have been extensively observed in animal models of fetal alcohol spectrum disorders (FASD). Here we use the Morris maze to test whether vinpocetine, a phosphodiesterase type 1 inhibitor, restores learning performance in rats exposed to alcohol during the third trimester equivalent of human gestation. Long Evans rats received ethanol (5g/kg i.p.) or saline on alternate days from postnatal day (P) 4 to P10. Two weeks later (P25), the latency to find a hidden platform was evaluated (2 trials per day spaced at 40-min inter-trial intervals) during 4 consecutive days. Vinpocetine treatment started on the first day of behavioral testing: animals received vinpocetine (20mg/kg i.p.) or vehicle solution every other day until the end of behavioral procedures. Early alcohol exposure significantly affected the performance to find the hidden platform. The average latency of ethanol-exposed animals was significantly higher than that observed for the control group. Treatment of alcohol-exposed animals with vinpocetine restored their performance to control levels. Our results show that inhibition of PDE1 improves learning and memory deficits in rats early exposed to alcohol and provide evidence for the potential therapeutic use of vinpocetine in FASD.
Filgueiras
Claudio C
CC
Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA 23298-0709, United States.
Krahe
Thomas E
TE
Medina
Alexandre E
AE
D000818:Animals; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1 / Q000037:antagonists & inhibitors*; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008431:Maternal-Fetal Exchange; D018782:Maze Learning / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D013997:Time Factors; D014748:Vinca Alkaloids / Q000494:pharmacology*
D014748:Vinca Alkaloids; D000431:Ethanol; C013983:vinpocetine; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1