The effect of amphetamine analogs on cleaved microtubule-associated protein-tau formation in the rat brain

Abstract

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 paramethoxyamphetamine (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 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. Keywords methamphetamine; 3,4-methylenedioxymethamphetamine; amphetamine; paramethoxyamphetamine; 5,7-dihydroxytryptamine; toxicity Methamphetamine (METH) and ±3,4-methylenedioxymethamphetamine (MDMA) are substituted phenylethylamines whose popularity among young adults continues to be a public

Chronic stress enhances methamphetamine‐induced extracellular glutamate and excitotoxicity in the rat striatum

“…In contrast to previously published observations using the acute toxic dosing model (i.e., four injections of METH every 2 h; Daberkow et al, 2005;Eyerman and Yamamoto, 2005;Friedman et al, 1998;Ricaurte et al 1982;Straiko et al, 2007;Wallace et al, 2001), METH administration to rats not exposed to CUS did not produce depletions in 5-HT tissue content (Fig. 3B).…”

Molecular and Cellular Mechanisms of Ecstasy-Induced Neurotoxicity: An Overview

“…However, in general, data referring to glial activation after neurotoxic regimens of MDMA are not consistent. A few studies report an increase in GFAP expression in the context of MDMA-induced neurotoxicity [286,292,293], whereas others do not [280,294,295]. Also, with the established 5-HT neurotoxicant, 5,7-DHT, data from different studies are also not consistent, with some studies revealing increased GFAP expression after neurotoxic regimens [280,296,297], whereas others do not [295,298].…”

“…A few studies report an increase in GFAP expression in the context of MDMA-induced neurotoxicity [286,292,293], whereas others do not [280,294,295]. Also, with the established 5-HT neurotoxicant, 5,7-DHT, data from different studies are also not consistent, with some studies revealing increased GFAP expression after neurotoxic regimens [280,296,297], whereas others do not [295,298]. It has been suggested that a lack of GFAP expression increase may be due to an insufficiently strong signal and that the use of this parameter for detecting degeneration of serotonergic termi- Decreased survival of neuronal precursors incorporated in the dentate gyrus of the HIP 5 mg/kg, i.p., eight doses, 1 day 14 [285] The table summarizes the findings on markers of neuronal degeneration in the rat brain after MDMA treatment.…”

Effects of MDMA on the Human Nervous System

“…However, when considering this line of reasoning, it is important to recognize that established 5-HT neurotoxins (e.g. 5, 7-DHT) also fail to consistently induce a glial reaction in brain regions distant from the site of intracerebral toxin injection (see Hardin et al, 1994;Frankfurt and Azmitia, 1984;Rowland et al, 1993;Bendotti et al, 1994;Straiko et al, 2007). Thus, in our view, rather than casting doubt on the neurotoxic potential of MDMA and other substituted amphetamines (e.g.…”