RESUMO
Immunological activation has been proposed to play a role in methamphetamine-induced dopaminergic terminal damage. In this study, we examined the roles of lipopolysaccharide, a pro-inflammatory and inflammatory factor, treatment in modulating the methamphetamine-induced nigrostriatal dopamine neurotoxicity. Lipopolysaccharide pretreatment did not affect the basal body temperature or methamphetamine-elicited hyperthermia three days later. Such systemic lipopolysaccharide treatment mitigated methamphetamine-induced striatal dopamine and 3,4-dihydroxyphenylacetic acid depletions in a dose-dependent manner. As the most potent dose (1 mg/kg) of lipopolysaccharide was administered two weeks, one day before or after the methamphetamine dosing regimen, methamphetamine-induced striatal dopamine and 3,4-dihydroxyphenylacetic acid depletions remained unaltered. Moreover, systemic lipopolysaccharide pretreatment (1 mg/kg) attenuated local methamphetamine infusion-produced dopamine and 3,4-dihydroxyphenylacetic acid depletions in the striatum, indicating that the protective effect of lipopolysaccharide is less likely due to interrupted peripheral distribution or metabolism of methamphetamine. We concluded a critical time window for systemic lipopolysaccharide pretreatment in exerting effective protection against methamphetamine-induced nigrostriatal dopamine neurotoxicity.
Assuntos
Gânglios da Base/efeitos dos fármacos , Dopaminérgicos/toxicidade , Lipopolissacarídeos/farmacologia , Metanfetamina/toxicidade , Neurônios/efeitos dos fármacos , Receptores Dopaminérgicos/efeitos dos fármacos , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Animais , Gânglios da Base/citologia , Gânglios da Base/metabolismo , Temperatura Corporal/efeitos dos fármacos , Temperatura Corporal/fisiologia , Dopamina/metabolismo , Dopaminérgicos/metabolismo , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Febre/metabolismo , Febre/fisiopatologia , Lipopolissacarídeos/imunologia , Masculino , Metanfetamina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Fármacos Neuroprotetores/imunologia , Fármacos Neuroprotetores/farmacologia , Receptores Dopaminérgicos/fisiologiaRESUMO
Major depression and dysthymia afflict a proportion of gravid and breast-feeding women. These women are frequently recommended on antidepressants to relieve their symptoms even if the drug effects on fetal growth and postnatal development are not completely known. In a previous study, we reported that prenatal bupropion exposure seemed to enhance the hedonic value of cocaine in adult mice. This study was undertaken to examine the dose-related effects for prenatal bupropion exposure on the stress susceptibility, cocaine-associated reinforcing property, and cocaine-induced behavioral sensitization in adult mice. Our results showed that various doses (ranging 12.5-50 mg/kg) of prenatal bupropion administration at the third trimester of pregnancy did not affect body weight of the adult mice. Bupropion administration at 50 mg/kg enhanced both ambulatory and rearing responses in the open field test. Moreover, bupropion administration (at 25 and 50 mg/kg) significantly decreased the numbers in open arm entry in the elevated plus maze test. Furthermore, prenatal bupropion treatment appeared to facilitate the cocaine-induced place preference in a sex-dependent manner. Finally, prenatal bupropion exposure (at 25 and 50 mg/kg) accelerated and elevated the development of cocaine-induced sensitization in locomotor activity. While the antidepressant and smoking-curbing effects of bupropion have been addressed in literature, we suggest that prenatal bupropion exposure could run a risk of enhancing individual's agitation, stress susceptibility and cocaine stimulating propensity in adulthood.