Actinomycin D blocks the reducing effect of dexamethasone on amphetamine and cocaine hypermotility in mice

1. The present study examined a time-course effect of dexamethasone (DEX) on amphetamine and cocaine-induced hypermotility in mice and the influence of actinomycin D (dactinomycin), a protein synthesis inhibitor, on DEX effects. 2. Amphetamine (5 mg/kg IP) and cocaine (10 mg/kg IP) increased markedly the locomotor activity of mice, whereas DEX alone (0.1-1.0-10 mg/kg IP) did not modify the activity of control mice. 3. DEX pretreatment 0, 15, 30, 60 and 120 min before amphetamine or cocaine strongly decreased both amphetamine and cocaine effects, but no dose-related effect was observed. 4. The time-course study performed with DEX revealed differences in its reducing effect on cocaine and amphetamine hypermotility when the groups of animals treated with the steroid immediately before the cocaine (or amphetamine) injection were compared to those treated with the steroid later (15, 30, 60 and 120 min). 5. Furthermore, actinomycin D was able to block the reducing effect of DEX on both amphetamine and cocaine hypermotility. 6. Therefore, considering that the administration time of the steroid seems to be an important factor for reducing both cocaine and amphetamine hypermotility, and actinomycin D was able to block the reducing effect of the steroid, our study suggests that DEX exerts its reducing effect through a genomic activation.