Abstract
The effects of rolipram, a selective inhibitor of phosphodiesterase 4, on the hyperlocomotion induced by several abused drugs(methamphetamine, morphine and phencyclidine)and a dopamine D1−receptor agonist(SKF81297;(±)−6−chloro−7, 8−dihydroxy−1−phenyl−2, 3, 4, 5−tetrahydro−1H−3−benzazepin hydrobromide)in mice were investigated.Methamphetamine(0.5−2.0 mg/kg), morphine(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 mg/kg)− and morphine(20 mg/kg)−induced hyperlocomotion, but not phencyclidine(5.0 mg/kg)−induced hyperlocomotion.These results suggest that cAMP in the brain is involved in methamphetamine− and morphine−induced hyperlocomotion, while the underlying mechanism(s)of phencyclidine−induced hyperlocomotion may be different from those of methamphetamine− and morphine−induced hyperlocomotion.It is well known that methamphetamine− and morphine−induced hyperlocomotion are mediated by the dopaminergic system and that interaction between postsynapic D1− and D2−receptors may play an important role in the expression of various dopamine−mediated behaviors.In the present study, SKF81297(10 mg/kg)−induced hyperlocomotion was significantly but not completely suppressed by the highest dose of rolipram(10 mg/kg).Therefore it is unlikely that postsynaptic D1−receptor−mediated functions are involved in the suppressive effects of rolipram on methamphetamine− and morphine−induced hyperlocomotion.These results suggest that rolipram may inhibit methamphetamine− and morphine−induced hyperlocomotion via increase cAMP levels at D2−receptors.
