A selective phosphodiesterase IV inhibitor, rolipram blocks both withdrawal behavioral manifestations, and c-Fos protein expression in morphine dependent mice.
We investigated the effect of rolipram, a selective phosphodiesterase IV inhibitor, on morphine dependence in mice. The withdrawal manifestations were significantly reduced in mice that were treated with rolipram in combination with morphine repeatedly, compared to the mice treated with morphine and saline. Immunohistochemical study of c-Fos protein revealed a significant increase in the protein expression, 1 h after naloxone induced withdrawal manifestations. A combination of rolipram and morphine treatment for 5 days prevented the increase of c-Fos protein expression. Acute rolipram treatment prior to the naloxone challenge had no effect. Repeated treatment with rolipram itself had no effect either on behavior, or on c-Fos protein expression. These results suggest that chronic rolipram treatment in combination with morphine in mice will abolish the development of morphine dependence and the expression of c-Fos protein induced by naloxone challenge.
Hamdy
M M
MM
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University, Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, 466-8560, Nagoya, Japan.
Mamiya
T
T
Noda
Y
Y
Sayed
M
M
Assi
A A
AA
Gomaa
A
A
Yamada
K
K
Nabeshima
T
T
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009021:Morphine Dependence / Q000188:drug therapy* / Q000378:metabolism; D009270:Naloxone / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000627:therapeutic use; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis* / Q000187:drug effects; D020889:Rolipram / Q000494:pharmacology*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*
D009292:Narcotic Antagonists; D010726:Phosphodiesterase Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D009270:Naloxone; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram