RESUMO
When burning crack cocaine, the pyrolysis of cocaine generates anhydroecgonine methyl ester (AEME). AEME has been shown to be highly neurotoxic but its effects on cognitive function and oxidative stress are still unknown. Thus, this study investigated the effects of AEME on spatial working memory and on parameters of oxidative stress in the prefrontal cortex, hippocampus, and striatum. First, 18 well-trained rats in 8-arm radial maze (8-RM) procedures received acute intracerebroventricular (icv) administration of AEME at doses of 10, 32, or 100 µg or saline (SAL) in a counterbalanced order and were tested 5 min later in 1-h delayed tasks in the 8-RM. Secondly, separated animals received acute icv administration of AEME at doses of 10 (n = 5), 32 (n = 5), or 100 µg (n = 5) or SAL (n = 5) for analysis of advanced oxidation protein products, thiobarbituric acid, catalase, glutathione peroxidase, and superoxide dismutase. A higher number of errors were seen in the 1-h post-delay performance after AEME 32 µg and AEME 100 µg when compared to SAL. In the striatum, animals receiving AEME 100 µg icv showed increased advanced oxidation protein products levels when compared to 10 µg, and also showed increased activity of glutathione peroxidase enzyme when compared to SAL but also comparing to AEME 32 µg and AEME 10 µg. These results showed that AEME impairs long-term spatial working memory and also induces greater protein oxidation and increased levels of antioxidant enzymes in the striatum.
Assuntos
Cocaína/análogos & derivados , Corpo Estriado/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Memória de Curto Prazo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Memória Espacial/efeitos dos fármacos , Animais , Cocaína/química , Cocaína/toxicidade , Corpo Estriado/metabolismo , Relação Dose-Resposta a Droga , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Transtornos da Memória/metabolismo , Memória de Curto Prazo/fisiologia , Estresse Oxidativo/fisiologia , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Ratos Wistar , Memória Espacial/fisiologiaRESUMO
This study correlated the executive frontal functions with blood alcohol concentration (BAC) in night drivers in a Brazilian city. Of 592 drivers randomly recruited between December 17, 2005 and May 5, 2006, during nighttime hours on main streets or avenues with intense vehicle traffic in Vitória, Brazil, 444 had the BAC determined by a portable digital breath alcohol analyzer and 389 were submitted to a frontal function examination by a frontal assessment battery (FAB). A high percentage (24.4%) of drivers presented alcohol in their blood. Most of these drivers were male (82%), and nearly half (43.7%) were young adults (aged between 20 and 30 years). The results showed an inverse relationship between the BAC and FAB total scores, with a higher BAC corresponding to a smaller FAB total score, delineating a progressive decrease in frontal function with increasing concentrations of alcohol. The most intriguing result was that alcohol-induced impairment on frontal executive function was particularly important in young adults, and more specifically in the motor programming subset of FAB, an executive function highly involved in driving skills. Considering the worldwide evidence of the high-risk involvement of youth in automobile crashes, the effects of alcohol in young adults need to be more thoroughly examined by cognitive studies, and more direct preventive solutions need to be taken focusing on this age range.
Assuntos
Consumo de Bebidas Alcoólicas , Condução de Veículo , Etanol/sangue , Função Executiva , Lobo Frontal/fisiologia , Adulto , Feminino , Humanos , Masculino , Adulto JovemRESUMO
RATIONALE: Delta(9)-Tetrahydrocannabinol (Delta(9)-THC) disrupts working memory. The prefrontal cortex (PFC) is involved in the processing of working memory, and its medial portion (mPFC) is part of a brain reward circuit as constituted by the mesocorticolimbic dopaminergic system. OBJECTIVE: This study examined the involvement of the mPFC in the effects of Delta(9)-THC on spatial working memory. METHODS: Ten male Wistar rats well-trained in a radial arm maze and with bilateral cannula implanted in the mPFC received Delta(9)-THC intra-cortically (Delta(9)-THC IC) at doses of 0 (VEH), 32, 100 or 180 microg, 5 min before a 5-s or a 1-h delayed task in order to measure a short- or long-term spatial working memory, respectively. By contrast, 11 other animals received Delta(9)-THC intraperitoneally (Delta(9)-THC IP) at doses of 0 (VEH), 0.32, 1 or 1.8 mg/kg, 30 min before a 5-s or a 1-h delayed task. Additionally, after a 15-day washout, the effect of an IP or IC pre-exposure of Delta(9)-THC was examined by repeating both dose-effect curves in a crossover order for the routes of administration. RESULTS: Delta(9)-THC IP produced significantly larger number of errors at doses of 0.32 or 1 mg/kg as compared to VEH in the 1-h post-delay performance. Delta(9)-THC 100 microg IC also produced significantly larger number of errors as compared to VEH and also to the other doses (32 or 180 microg) IC in the 1-h post-delay performance. Previous exposure to Delta(9)-THC IP or IC did not significantly affect the disruptive effect of this cannabinoid. CONCLUSIONS: Delta(9)-THC administered directly in the mPFC impaired 1-h delayed task in the radial arm maze in a manner similar to that observed for its systemic administration, suggesting that the mPFC is involved in the disruptive effects of Delta(9)-THC on spatial working memory.