Fig. 4.

Time course of the effects of pretreatment with JHW007 in combination with cocaine on locomotor activity in mice. Ordinates: horizontal locomotor activity counts/minute. Abscissae: treatment condition, vehicle (V), or cocaine dose in milligrams per kilograms. JHW007 was administered at 10 minutes, 1, 2, 4.5, 8, and 24 hours before administration of different doses of cocaine (5.0–60 mg/kg). Each point represents the average (+ S.E.M.) rate in counts/minute determined in six to eight mice for a time period of 90 minutes. The combination effects of JHW007 and cocaine at 24 hours were determined under three different experimental conditions where vehicle or 10 mg/kg JHW007 was injected either in the experimental chamber (EC), home cage in the laboratory (HC), or in the housing room (HR) in the animal facility. Note that at time points of 10 minutes to 8 hours, JHW007 alone failed to significantly alter locomotor behavior, whereas JHW007 alone administered after 8 hours produced cocaine-like increases in locomotor activity, particularly under the HC and HR conditions at 24 hours. Administration of 10 mg/kg JHW007 at pretreatment times of 10 minutes to 8 hours fully antagonized the locomotor-stimulant effects of cocaine. At 24 hours after JHW007 administration, the locomotor-stimulant effects of cocaine was potentiated, i.e., the cocaine dose-effect was shifted upward and to the left under both HC and HR conditions. *P < 0.05 versus vehicle + vehicle; #P < 0.05 versus vehicle + cocaine.