Jpn. J. Pharmacol. 83 (2), 113-118 (2000)

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

Tomohisa Mori¹, Jun Baba¹, Yasuyuki Ichimaru^1,* and Tsutomu Suzuki<sup>2


1</sup>PharmaceuticalﾊResearch Center, Meiji Seika Kaisha, Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama 222-8567, Japan
²Departmentﾊof Toxicology, School of Pharmacy, Hoshi University, Shinagawa-ku, Tokyo 142-8501, Japan
*ﾊTo whom correspondence should be addressed.

Abstract: The effects of rolipram, a selective inhibitor of phosphodiesteraseﾊ4, on the hyperlocomotion induced by several abused drugs (methamphetamine, morphine and phencyclidine) and a dopamineﾊD₁-receptor agonist (SKF81297; (ｱ)-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ﾊmg/kg), morphine (5.0-20ﾊmg/kg), phencyclidine (1.25-5.0ﾊmg/kg) and SKF81297 (2.5-10ﾊmg/kg) each induced dose-dependent hyperlocomotion. A low dose (1.0ﾊmg/kg) or moderate dose (3.2ﾊmg/kg) of rolipram suppressed methamphetamine (2.0ﾊmg/kg)- and morphine (20ﾊmg/kg)-induced hyperlocomotion, but not phencyclidine (5.0ﾊ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ﾊD₁- and D₂-receptors may play an important role in the expression of various dopamine-mediated behaviors. In the present study, SKF81297 (10ﾊmg/kg)-induced hyperlocomotion was significantly but not completely suppressed by the highest dose of rolipram (10ﾊ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.

Keywords: Rolipram, Methamphetamine, Phencyclidine, Morphine, SKF81297