Effects of rolipram, a selective inhibitor of phosphodiesterase 4, on hyperlocomotion induced by several abused drugs in mice

The effects of rolipram, a selective inhibitor of phosphodiesterase 4, on t he hyperlocomotion induced by several abused drugs (methamphetamine, morphi ne and phencyclidine) and a dopamine D-1-receptor agonist (SKF81297; (+/-)- 6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepin hydrobro mide) in mice were investigated. Methamphetamine (0.5 - 2.0 mg/kg), morphin e (5.0 - 20 mg/kg), phencyclidine (1.25 - 5.0 mg/kg) and SKF81297 (2.5 - 10 mg/kg) each induced dose-dependent hyperlocomotion. A low dose (1.0 mg/kg) or moderate dose (3.2 mg/kg) of rolipram suppressed methamphetamine (2.0 m g/kg)- and morphine (20 mg/kg)-induced hyperlocomotion, but not phencyclidi ne (5.0 mg/kg)-induced hyperlocomotion. These results suggest that cAMP in the brain is involved in methamphetamine- and morphine-induced hyperlocomot ion, while the underlying mechanism(s) of phencyclidine-induced hyperlocomo tion may be different from those of methamphetamine- and morphine-induced h yperlocomotion. It is well known that methamphetamine- and morphine-induced hyperlocomotion are mediated by the dopaminergic system and that interacti on between postsynaptic D-1- and D-2-receptors may play an important role i n the expression of various dopamine-mediated behaviors. In the present stu dy, SKF81297 (10 mg/kg)-induced hyperlocomotion was significantly but not c ompletely suppressed by the highest dose of rolipram (10 mg/kg). Therefore it is unlikely that postsynaptic D-1-receptor-mediated functions are involv ed in the suppressive effects of rolipram on methamphetamine- and morphine- induced hyperlocomotion. These results suggest that rolipram may inhibit me thamphetamine- and morphine-induced hyperlocomotion via increase cAMP level s at D-2-receptors.