Motor depressant effects of systemically administered polyamines in mice: Involvement of central NMDA receptors

The systemic administration of polyamines (s.c.) produced a dose-dependent motor depression. With high doses the depressant effect was long-lasting and the animals showed signs of toxicity. ED50 values for spermine, spermidine and putrescine were 38, 90 and 251 mg/kg respectively. The motor depression induced by the systemic administration of N-methyl-D-aspartate (NMDA; 25 mg/kg i.p.) was used as a model for studying the interactions between polyamines and the NMDA receptor. Results indicate that (1) the motor effects elicited by NMDA are very similar to those induced by polyamines at ED50 doses; (2) polyamines, even at non-active doses, potentiate the motor depressant effect induced by NMDA; (3) the NMDA receptor antagonist, (5R,10S)-(+)-5-methyl-10,11-dihydro-5H- dibenzo[a,d]cyclohepten-5,10-imine (MK-801; 0.5 mg/kg i.p.), abolishes the depressant effect elicited by NMDA and by polyamines, even at toxic doses; (4) amphetamine (1.5 mg/kg i.p.) does not counteract the motor depressant effects of NMDA or polyamines. On the other hand, the adenosine receptor antagonist, theophylline (30 mg/kg i.p.), counteracts NMDA- but not polyamine-induced motor depression. The concentration of polyamines in the brain is modified after their systemic administration at high doses and at the ED50 dose of putrescine. In conclusion, the data suggest that the NMDA receptor could be a target mediating the motor effect elicited by polyamines. They also show that the quantitative analysis of the motor effects elicited by non-convulsant doses of NMDA might be a powerful tool for studying in vivo the interaction between neurotransmission systems involved in the regulation of motor activity.This work was supported by grants SAF, 92-0913 (CICYT) and FIS, 93/0350 from the Spanish Government. The skillful technical assistance of L. Campa is acknowledged. Statistical advice from M. Martfn (UAB