TY  - JOUR
PY  - 2012//
TI  - The neurotoxicity of anhydroecgonine methyl ester, a crack cocaine pyrolysis product
JO  - Toxicological sciences
A1  - Garcia, Raphael Caio Tamborelli
A1  - Dati, Livia Mendonça Munhoz
A1  - Fukuda, Suelen
A1  - Torres, Larissa Helena Lobo
A1  - Moura, Sidnei
A1  - de Carvalho, Nathalia Delazeri
A1  - Carrettiero, Daniel Carneiro
A1  - Camarini, Rosana
A1  - Levada-Pires, Adriana Cristina
A1  - Yonamine, Mauricio
A1  - Neto, Osvaldo Negrini
A1  - Abdalla, Fernando Maurício Francis
A1  - Sandoval, Maria Regina Lopes
A1  - Afeche, Solange Castro
A1  - Marcourakis, Tania
SP  - 223
EP  - 234
VL  - 128
IS  - 1
N2  - Smoking crack cocaine involves the inhalation of cocaine and its pyrolysis product, anhydroecgonine methyl ester (AEME). There is evidence that cocaine is neurotoxic, but the neurotoxicity of AEME has never been evaluated. AEME seems to have cholinergic agonist properties in the cardiovascular system; however, there are no reports on its effects in the central nervous system. The aim of this study was to investigate the neurotoxicity of AEME and its possible cholinergic effects in rat primary hippocampal cell cultures that were exposed to different concentrations of AEME, cocaine and to a cocaine-AEME combination. We also evaluated the involvement of muscarinic cholinergic receptors in the neuronal death induced by these treatments using concomitant incubation of the cells with atropine. Neuronal injury was assessed using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. The results of the viability assays showed that AEME is a neurotoxic agent that has greater neurotoxic potential than cocaine after 24 and 48 hours of exposure. We also showed that incubation for 48 hours with the combination of both compounds in equipotent concentrations had an additive neurotoxic effect. Although both substances decreased cell viability in the MTT assay, only cocaine increased LDH release. Caspase 3 activity was increased after incubation with 1 mM cocaine and after 6 hours of 0.1 and 1 mM AEME exposure. Atropine prevented the AEME-induced neurotoxicity, which suggests that muscarinic cholinergic receptors are involved in AEME's effects. In addition, binding experiments confirmed that AEME has an affinity for muscarinic cholinergic receptors. Nevertheless, atropine was not able to prevent the neurotoxicity produced by cocaine and the cocaine-AEME combination, suggesting that these treatments activated other neuronal death pathways. Our results suggest a higher risk for neurotoxicity after smoking crack cocaine than after cocaine use alone.<p />  <p>Language: en</p>
LA  - en
SN  - 1096-6080
UR  - http://dx.doi.org/10.1093/toxsci/kfs140
ID  - ref1
ER  -