RESUMO
Pretreatment of rats with the noradrenergic neurotoxin DSP-4 selectively reduced regional levels of noradrenaline in the brain by more than 75%, and decreased the concentration of endogenous DA in microdialysates of the caudate nucleus and nucleus accumbens by 52% and 28%, respectively. Results support the hypothesis that central noradrenergic mechanisms facilitate nigrostriatal and mesolimbic dopamine transmission in vivo.
Assuntos
Benzilaminas/farmacologia , Encéfalo/metabolismo , Corpo Estriado/metabolismo , Dopamina/metabolismo , Sistema Límbico/metabolismo , Norepinefrina/metabolismo , Substância Negra/metabolismo , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Núcleo Caudado/efeitos dos fármacos , Núcleo Caudado/metabolismo , Cerebelo/efeitos dos fármacos , Cerebelo/metabolismo , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Corpo Estriado/efeitos dos fármacos , Diálise/métodos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Ácido Hidroxi-Indolacético/metabolismo , Sistema Límbico/efeitos dos fármacos , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Especificidade de Órgãos , Ratos , Ratos Endogâmicos , Valores de Referência , Serotonina/metabolismo , Substância Negra/efeitos dos fármacos , Simpatomiméticos/farmacologiaRESUMO
Six pairs of female squirrel monkeys were given a daily intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 9-14 days, beginning the same day on which they received either a bilateral 6-hydroxydopamine lesion or a sham lesion of the locus coeruleus. Sham animals developed typical parkinsonian signs (i.e. tremor, bradykinesia, hypokinesia and reduced blink rate) which largely recovered by six to nine weeks after the start of MPTP treatment. At nine weeks, post mortem levels of striatal dopamine in these same animals were partially reduced (by 45%), and this only in the putamen, compared to values obtained from three non-operated, normal control animals. Additionally, histological examination revealed a moderate loss of neuronal cell bodies in the substantia nigra, pars compacta. In marked contrast, the locus coeruleus-lesioned monkeys exhibited little or no recovery from the parkinsonian signs induced by MPTP. Post mortem examination of these animals revealed profound decreases in caudate (by 84%) and putamen (by 91%) dopamine content, and severe neuronal cell loss in the substantia nigra pars compacta of all animals. These neurological, biochemical and histological assessments indicate that lesioning of the locus coeruleus impairs the recovery which usually occurs from the parkinsonian manifestations induced by MPTP in squirrel monkeys. The results support the hypothesis that deficient locus coeruleus noradrenergic mechanisms underlie the progression of Parkinson's disease.
Assuntos
Corpo Estriado/fisiologia , Dopamina/metabolismo , Locus Cerúleo/fisiopatologia , Atividade Motora , Neurônios/fisiologia , Doença de Parkinson Secundária/fisiopatologia , Substância Negra/patologia , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Estimulação Acústica , Animais , Corpo Estriado/patologia , Eletrofisiologia/métodos , Feminino , Locomoção , Locus Cerúleo/patologia , Locus Cerúleo/fisiologia , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/patologia , Estimulação Física , Valores de Referência , Saimiri , Tremor/fisiopatologiaRESUMO
Bilateral 6-hydroxydopamine lesions of the rat locus coeruleus (a) depleted forebrain norepinephrine levels by 67%, (b) reduced the basal release of dopamine in the nucleus accumbens and caudate nucleus by 26% and 19%, respectively, and (c) reduced (+)-amphetamine-induced release in the nucleus accumbens and caudate nucleus. The locus coeruleus appears to exert a tonic excitatory influence on striatal and limbic dopamine release in vivo.
