Haloperidol and restraint differently inhibit the induction of sensitization to the ambulation-increasing effect of methamphetamine in mice.

Haloperidol (HPD: 0.4 mg/kg, sc) completely abolished not only the ambulatory stimulation by methamphetamine (MAP: 2 mg/kg, sc) but also the induction and expression of MAP sensitization in the combined administration schedule. HPD also significantly reduced the induction of MAP sensitization when the mice were treated with HPD at 1/12, 1/4, 1, 2, 3, 4 or 5 hr but not at 1/2 hr or later than 6 hr, after each administration of MAP. The inhibition by the 3-hr post-treatment with HPD was as strong as that by the combined administration. On the other hand, a restraint of abulation for 3 hr (putting the mouse in a small jar) significantly inhibited the induction of MAP sensitization when it was started at 0/4 hr, but not at 1/2-6 hr, after each MAP administration. The inhibitory effects of restraint, starting at 0-1/4 hr, were almost equivalent to those of the post-treatments with HPD at the same times. The post treatments with HPD + restraint showed similar inhibitory effects on MAP sensitization to those of HPD alone. The repeated administration of saline together with post-treatment with either HPD, restraint or HPD + restraint did not change MAP sensitivity. These results suggest that a couple of free movement in the activity cage and stimulation of dopamine receptors for longer than 1/2 hr immediately after administration of MAP, and an agonistic effect on dopamine receptors during 1-5 hr after MAP are responsible for perfect induction of the MAP sensitization in terms of ambulation in mice.