Inhibition of behavioral effects of cocaine by actinomycin D in rats

Abstract

Interactions of actinomycin D (AD, 25 micrograms--50 micrograms/kg intraperitoneally, i.p., or 1 microgram intracerebroventricularly, i.c.v.) with repeated cocaine administration (15 mg/kg i.p. twice daily at 8-hr intervals) were investigated on the spontaneous motor activity (SMA) and stereotypy (ST) in rats. Following repeated injections of cocaine in combination with saline (i.p. or i.c.v.), both SMA and ST were gradually increased to their peaks on day 9, then decreased up to the day 19 and thereafter maintained at higher than normal levels. Given along with cocaine or saline, AD (i.p. or i.c.v.) caused gradual and significant decreases of SMA and ST. On stopping AD (i.p. on day 5 and i.c.v. on day 9) injection, both SMA and ST increased again. After stopping its i.c.v. injection both behaviors were increased to their peaks on day 10, then gradually decreased to and maintained at slightly higher than normal levels on day 18 onwards. The possible mechanisms of actions of AD as an inhibitor of cocaine-induced behavioral effects have been discussed.