Phosphodiesterase type 4 inhibition does not restore ocular dominance plasticity in a ferret model of fetal alcohol spectrum disorders.
BACKGROUND
There is growing evidence that deficits in neuronal plasticity account for some of the neurological problems observed in fetal alcohol spectrum disorders (FASD). Recently, we showed that early alcohol exposure results in a permanent impairment in visual cortex ocular dominance (OD) plasticity in a ferret model of FASD. This disruption can be reversed, however, by treating animals with a Phosphodiesterase (PDE) type 1 inhibitor long after the period of alcohol exposure.


OBJECTIVE
Because the mammalian brain presents different types of PDE isoforms we tested here whether inhibition of PDE type 4 also ameliorates the effects of alcohol on OD plasticity.


METHODS
Ferrets received 3.5 g/Kg alcohol i.p. (25% in saline) or saline as control every other day between postnatal day (P) 10 to P30, which is roughly equivalent to the third trimester equivalent of human gestation. Following a prolonged alcohol-free period (10 to 15 days), ferrets had the lid of the right eye sutured closed for 4 days and were examined for ocular dominance changes at the end of the period of deprivation.


RESULTS
Using in vivo electrophysiology we show that inhibition of PDE4 by rolipram does not restore OD plasticity in alcohol-treated ferrets.


CONCLUSIONS
This result suggests that contrary to PDE1, PDE4 inhibition does not play a role in the restoration of OD plasticity in the ferret model of FASD.
Krahe
Thomas E
TE
Department of Anatomy and Neurobiology, Virginia Commonwealth University Medical Center, Richmond, Virginia 23298-0709, USA.
Paul
Arco P
AP
Medina
Alexandre E
AE
D000818:Animals; D023882:Dominance, Ocular / Q000187:drug effects*; D005260:Female; D005289:Ferrets; D063647:Fetal Alcohol Spectrum Disorders / Q000188:drug therapy*; D009473:Neuronal Plasticity / Q000187:drug effects*; D058988:Phosphodiesterase 4 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011247:Pregnancy; D020889:Rolipram / Q000494:pharmacology / Q000627:therapeutic use*
D058988:Phosphodiesterase 4 Inhibitors; D010726:Phosphodiesterase Inhibitors; D020889:Rolipram