The effects of a selective cAMP phosphodiesterase inhibitor, rolipram, on methamphetamine-induced behavior.
The effects of rolipram, a selective cAMP phosphodiesterase inhibitor, on locomotor activity, rearing, and stereotyped behavior (sniffing, repetitive head movements) induced by methamphetamine (MAP) over 1 hour were investigated in rats. Coadministration of rolipram (4 mg/kg IP) significantly attenuated the responses of locomotor activity, rearing and repetitive head movements to MAP (2,4 or 8 mg/kg IP). Rolipram (0.5, 1, 2, or 4 mg/kg IP) dose-dependently inhibited locomotor hyperactivity and rearing induced by 4 mg/kg of MAP. The rearing was completely inhibited by 4 mg/kg of rolipram, whereas the maximal inhibition of the locomotor hyperactivity was about 50%. However, rolipram did not alter MAP-induced sniffing and repetitive head movements. These results indicate that there is heterogeneity in the response of MAP-induced behavior to rolipram, suggesting that MAP-induced behavioral alteration may be partly regulated by cAMP levels in the brain.
Iyo
M
M
Division of Drug Dependence and Psychotropic Drugs Clinical Research, National Institute of Mental Health, National Center of Neurology and Psychiatry, Chiba, Japan.
Maeda
Y
Y
Inada
T
T
Kitao
Y
Y
Sasaki
H
H
Fukui
S
S
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D020889:Rolipram
D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D008694:Methamphetamine; D000242:Cyclic AMP; D020889:Rolipram