Premium
Striatal and cortical NMDA receptors are altered by a neurotoxic regimen of methamphetamine
Author(s) -
Eisch Amelia J.,
O'Dell Steven J.,
Marshall John F.
Publication year - 1996
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/(sici)1098-2396(199603)22:3<217::aid-syn3>3.0.co;2-f
Subject(s) - nmda receptor , methamphetamine , striatum , nucleus accumbens , chemistry , glutamate receptor , glutamatergic , dopamine , amphetamine , medicine , receptor , endocrinology , pharmacology , neuroscience , psychology , biochemistry
Methamphetamine (m‐AMPH) treatment produces long‐lasting damage to striatal andcortical monoaminergic terminals and may also injure nonmonoaminergic cortical neurons.Evidence suggests that both dopamine (DA) and glutamate (GLU) play crucial roles inproducing this damage. We used quantitative autoradiography to examine[ 3 H]mazindol ([ 3 H]MAZ) binding to striatal DA transportersand [ 3 H]GLU binding to N‐methyl‐D‐aspartate (NMDA) receptors in thestriatum and cortex 1 week and 1 month after a neurotoxic regimen of m‐AMPH. Ratsreceived m‐AMPH (4 mg/kg) or saline (SAL) (1 ml/kg) in four s.c. injections separated by 2h intervals. One week after m‐AMPH, the ventral and lateral sectors of the striatum showedthe greatest decreases in both [ 3 H]MAZ and [ 3 H]GLU binding,while the nucleus accumbens (NA) showed no significant decreases. One month afterm‐AMPH, striatal [ 3 H]MAZ binding was still significantly decreased, whileNMDA receptor binding had recovered. Surprisingly, the parietal cortex showed am‐AMPH‐induced increase in NMDA receptor binding in layers II/III and IV 1 week afterm‐AMPH and only in layers II/III 1 month after m‐AMPH. The prefrontal cortex showed nom‐AMPH‐induced changes in NMDA receptor binding at either time point. This is the firstdemonstration that a regimen of m‐AMPH that results in long‐lasting damage to DA terminalscan alter forebrain NMDA receptor binding. Thus, repeated m‐AMPH treatments may producechanges in glutamatergic transmission in selected striatal and cortical regions. © 1996Wiley‐Liss, Inc.