Effects of Rolipram, a Selective Inhibitor of Phosphodiesterase 4, on Hyperlocomotion Induced by Several Abused Drugs in Mice

• Published in: Japanese Journal of Pharmacology Vol. 83; no. 2; pp. 113 - 118
• Main Authors: Mori, Tomohisa, Baba, Jun, Ichimaru, Yasuyuki, Suzuki, Tsutomu
• Format: Journal Article
• Language: English; Japanese
• Published: Japan The Japanese Pharmacological Society 2000
• Subjects: 3',5'-Cyclic-AMP Phosphodiesterases - antagonists & inhibitors; Animals; Benzazepines - pharmacology; Cyclic Nucleotide Phosphodiesterases, Type 4; Dopamine Agents - pharmacology; Locomotion - drug effects; Male; Methamphetamine; Methamphetamine - pharmacology; Mice; Morphine; Morphine - pharmacology; Phencyclidine; Phencyclidine - pharmacology; Phosphodiesterase Inhibitors - pharmacology; Rolipram; Rolipram - pharmacology; SKF81297; Morphine; Rolipram; Phencyclidine; SKF81297; Methamphetamine
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)30605-5

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-lH-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 postsynaptic 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.