STRIATAL AND CORTICAL NMDA RECEPTORS ARE ALTERED BY A NEUROTOXIC REGIMEN OF METHAMPHETAMINE

Methamphetamine (m-AMPH) treatment produces long-lasting damage to str iatal and cortical monoaminergic terminals and may also injure nonmono aminergic cortical neurons. Evidence suggests that both dopamine (DA) and glutamate (GLU) play crucial roles in producing this damage. We us ed quantitative autoradiography to examine [H-3]mazindol ([H-3]MAZ) bi nding to striatal DA transporters and [H-3]GLU binding to N-methyl-D-a spartate (NMDA) receptors in the striatum and cortex 1 week. and 1 mon th after a neurotoxic regimen of m-AMPH. Rats received m-AMPH (4 mg/kg ) or saline (SAL) (1 ml/kg) in four s.c. injections separated by 2 h i ntervals. One week after m-AMPH, the ventral and lateral sectors of th e striatum showed the greatest decreases in both [H-3]MAZ and [H-3]GLU binding, while the nucleus accumbens (NA) showed no significant decre ases. One month after m-AMPH, striatal [H-3]MAZ binding was still sign ificantly decreased, while NMDA receptor binding had recovered. Surpri singly, the parietal cortex showed a m-AMPH-induced increase in NMDA r eceptor binding in layers II/III and IV 1 week after m-AMPH and only i n layers II/III 1 month after m-AMPH. The prefrontal cortex showed no m-AMPH-induced changes in NMDA receptor binding at either time point. This is the first demonstration that a regimen of m-AMPH that results in long-lasting damage to DA terminals can alter forebrain NMDA recept or binding. Thus, repeated m-AMPH treatments may produce changes in gl utamatergic transmission in selected striatal and cortical regions. (C ) 1996 Wiley-Liss, Inc.