Methamphetamine-induced striatal dopamine release, behavior changes and neurotoxicity in BALB/c mice

The behaviors associated with the neurotoxic effects of methamphetamine wer e evaluated in BALB/c mice. Hyperthermia and behavioral observations were m easured 60 min after each subcutaneous injection of methamphetamine (4 x 4 or 8 mg/kg) or saline, each given 2 h apart. The behavioral observations in cluded stereotyped behaviors, incidence of hemorrhage in breast, salivation and self-injurious behavior (SIB). Repeated administration of methamphetam ine produced these behavioral changes and hyperthermia, but resulted in hyp othermia by the final injection (8 mg/kg). In addition, the methamphetamine treatment induced a long-lasting dopamine depletion of similar magnitude i n the 4 and 8 mg/kg-treated animals. In a time course study striatal monoam ine levels were measured 60 min after each injection of these doses. The fi rst and second injections of methamphetamine (8 mg;kg) produced a drastic i ncrease in striatal 3-methoxytyramine; this failed to occur after the third or fourth injection of the same dose. In contrast? 4 mg/kg of methamphetam ine also produced an increase in 3-methoxytyramine after the second and thi rd injections of the drug and, in this case, these were maintained for the duration of the treatment. Striatal 3,4-dihydroxyphenylacetic acid levels a lso drastically decreased following both doses of methamphetamine, suggesti ng inhibition of monoamine oxidase in striatum. Moreover, a single injectio n of methamphetamine increased striatal 2,3dihydroxybenzoic acid formation. These results suggest that the incidence of hyperthermia, SIB and striatal dopamine neurotoxicity are closely linked to striatal dopamine release and inhibition of monoamine oxidase produced by methamphetamine in BALB/c mice. (C) 2000 ISDN. Published by Elsevier Science Ltd. All rights reserved.