Inhibitory effect of restraint on induction of behavioral sensitization to methamphetamine and cocaine in mice.

Repeated intermittent (generally 3-day intervals) administrations of methamphetamine (MAP: 2 mg/kg, SC) or cocaine (COC: 20 mg/kg, SC) induced sensitization to the ambulation-increasing effect of individual drug in mice. The induction of MAP and COC sensitization was inhibited when restraint of the mouse (putting the mouse in a jar of 6 cm in diameter for 3 and 2 h after administration of MAP and COC, respectively) was started immediately after each drug administration. Furthermore, the induction of sensitizations to MAP and COC was significantly reduced when the restraint was started within 1/4 h and 1/6 h after the administration of MAP and COC, respectively, whereas the restraint starting thereafter did not affect the induction of sensitization. The three times repeated administrations of saline with or without restraint did not significantly change the sensitivities to MAP and COC. The ambulation-increasing effects of MAP and COC reached the peak at approximately 2/3 and 1/2 h, respectively, and persisted for 3 and 2 h after the administration. The present results suggest that, to completely induce sensitization to MAP and COC in terms of ambulation, the mice must freely move for at least half of the latency to their peak effects.