The effect of amphetamine analogs on cleaved microtubule-associated protein-tau formation in the rat brain.
The present study quantified the cleaved form of the microtubule-associated protein tau (cleaved MAP-tau, C-tau), a previously demonstrated marker of CNS toxicity, following the administration of monoamine-depleting regimens of the psychostimulant drugs amphetamine (AMPH), methamphetamine (METH), +/-3,4-methylenedioxymethamphetamine (MDMA), or para-methoxyamphetamine (PMA) in an attempt to further characterize psychostimulant-induced toxicity. A dopamine (DA)-depleting regimen of AMPH produced an increase in C-tau immunoreactivity in the striatum, while a DA- and serotonin (5-HT)-depleting regimen of METH produced an increase in the number of C-tau immunoreactive cells in the striatum and CA2/CA3 and dentate gyrus regions of the hippocampus. MDMA and PMA, two psychostimulant drugs that produce selective 5-HT depletion in the striatum, had no effect on C-tau immunoreactivity in the striatum or hippocampus. Furthermore, 5,7-dihydroxytryptamine (5,7-DHT), an established 5-HT selective neurotoxin, did not produce an increase in C-tau immunoreactivity. Dual fluorescent immunocytochemistry with antibodies to glial fibrillary acidic protein (GFAP) and C-tau indicated that C-tau immunoreactivity was present in astrocytes, not neurons, suggesting that increased C-tau may be an alternative indicator of reactive gliosis. The present results are consistent with previous findings that the DA-depleting psychostimulants AMPH and METH produce reactive gliosis whereas the 5-HT-depleting drugs MDMA and PMA, as well as the known 5-HT selective neurotoxin 5,7-DHT, do not produce an appreciable glial response.
Straiko
M M W
MM
Neuroscience Graduate Program, University of Cincinnati, Cincinnati, OH 45267, USA.
Coolen
L M
LM
Zemlan
F P
FP
Gudelsky
G A
GA
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D003627:Data Interpretation, Statistical; D004298:Dopamine / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis*; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D018490:Serotonin Agents / Q000494:pharmacology; D016875:tau Proteins / Q000096:biosynthesis*
D000662:Amphetamines; D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; D018490:Serotonin Agents; D016875:tau Proteins; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D008694:Methamphetamine; D018817:N-Methyl-3,4-methylenedioxyamphetamine; C100230:4-methoxyamphetamine; D004298:Dopamine