Effects on monoamine levels in rat CNS after chronic administration of cocaine / Efecto de la administración crónica de cocaína sobre los niveles de monoaminas en el sistema nervioso central de la rata

We have previously reported time dependent and dose dependent changes in the rat dopaminergic receptor system following chronic administration of cocaine (upregulation of cacaina, D1, and DA-uptake sites). We have now evaluated the effects of chronic cacaine exposure on the central catecholamine/indolamine neurotransmitter systems. Groups of rats were injected with cocaine (15 mg/kg, i.p, b.i.d.) or saline for 1,3,7,14 or 21 days. Cortical and striatal tissues were analysed for morepinephrine, dopamine, serotomin and their primary metabolites using a HPLC-ECD method. Chronic administration of cacaine did not change the cortical and striatal concentrations of the neurotransmitters under study; except, for a transient increase in the cortical MHPG concentration on day 3. These results suggest that changes in the dopaminergic receptor system following chronic cocaine exposure are not to changes in the neurotransmitter concentrations

Intoxicación crónica con manganeso: cuantificación autorradiográfica de los receptores colinérgicos muscarínicos en el cerebro de ratón / Chronic manganese poisoning: autoradiograohic cuantitation of muscarinic cholinergic receptors in mouse brain

El tratamiento crónico con cloruro de manganeso (5 mg Mn/kg/día), durante 9 semanas, no afectó la unión del radioligando [3H]-quinuclidinil benzilato a los receptores colinérgicos muscarínicos en el cerebro de ratón. Mediante técnica autorradiográfica se determinó la localización anatómica precisa de los receptores y se procedió a la cuantificació de los mismos en los cortes coronales del bulbo olfatorio y del cerebro medio. A la luz de los resultados obtenidos podemos concluir que, en nuestras condiciones experimentales, no se producen alteraciones en la densidad de los receptores colinérgicos muscarínicos en el cerebro de ratones intoxicados con manganeso

Role of methamphetamine metabolism in the development of CNS tolerance the drug / Rol del metabolismo de la metanfetamina en el desarrollo de tolerancia del sistema nervioso central a los efectos de la droga

We have previously observed that pretreatment with increasing doses of methamphetamine (METH) atteniates the effects of METH on the dopaminergic and serotonergic systems as compared with the ones observed in nonpretreated controls. In order to understand the mechanism of this tolerance, untreated rats pretreated with METH (daoly doses of 5.0, 7.5; and 10 mg/kg, s.c., at 6h intervals with a 24h drug-free period between each dose) were challenged with the administration of 5 doses of METH (15 mg/kg, s.c., at 6h intervals). The metabolism of METH in brain, liver and blood was studied measuring the concentration of METH and its metabolites 2,4,6,8 and 10h after the last dose by gas chromatography/mass spectrometry techniques. The forebrain concentrations of METH in the pretreated animals were significanthy lower than those observed in the forebrain of naive animals. Liver concentrations of METH in the pretreated animals were not significantly modified as compared to the ones of naive animals, but in liver amphetamine and the p-hydroxylated metabolites, p-hydroxyamphetamine (p-OH-AMP) and p-hydroxymethamphetamine (p-OH-METH), were significantly greater than those observed in the naive group. Bloo levels of METH, AMP and their p-hydroxylated metabolites were also greater in the pretreated animals. The involvement of an altered distribution of methamphetamine in the CNS and the development of tolerance is discussed