Methamphetamine処置ラットのStereotypyおよび自発運動におよぼすReserpine連用後のα-Methyl-p-tyosineの効果

Abstract

Previously we have found such "bizarre stereotypy" as persistent and bloody biting activity at the legs or the tail of himself or of the cage mate given methamphetamine (MAPT, 10 mg/kg) 24 hrs-48 hrs after long term-administration of reserpine (RE). The present investigation examined the effect of inhibition of dopamine synthesis in brain on MAPT-induced "bizarre stereotypy" and hypermotility of RE-treated rats. Male albino Wistar rats aged 4 weeks were injected intraperitoneally with RE (1.25 mg/kg) or 0.9% saline solution (1.25 ml/kg) every two days for 13 days. Twenty-two hrs after the last injection, rats received alpha-methyl-para-tyrosine ( alpha-MPT, 50 mg/kg, 125 mg/kg, 250 mg/kg i.p.) or its vehicle (1 ml/kg i.p.) and 2 hrs later, MAPT. MAPT induced continuous licking and biting at the metal wire of the cage floor in saline-treated rats and also "bizarre stereotypy" in RE-treated rats, but these activities were completely suppressed by pretreatment of alpha-MPT in each dose given (especially in 125 mg/kg, 250 mg/kg). Pertaining to the locomotor activities of saline-treated rats, the horizontal movements were especially enhanced by MAPT, however, the vertical movements remained unchanged. Alpha-MPT partially inhibited such horizontal movements while it potentiated the vertical movements. Locomotor activities of RE-treated rats were depressed one day after the last injection of RE, however, after the MAPT, these activities counts were increased considerably and were also higher in comparison to the counts of saline-treated rats given MAPT. These hypermotilities in RE-treated rats were partially antagonized by pretreatment with alpha-MPT. It is suggested that MAPT-induced "bizarre stereotypy" of RE-treated rats is mediated by the accelerative effect of RE on MAPT-induced dopamine synthesis, while MAPT-induced hypermotility of RE-treated rats is partially related to such an acceleration of dopamine synthesis.