RESUMO
The purpose of this study was to obtain direct evidence that the nigrostriatal dopamine (DA) pathway modulates the metabolism of striatal dynorphin and [Met5]-enkephalin. This was achieved by repeated injections of apomorphine (APO) or D-amphetamine (AMP) in unilateral nigral 6-hydroxydopamine (6-OHDA)-lesioned rats. Three weeks after a 6-OHDA lesion, dynorphin A(1-8)-like immunoreactivity (DN-LI) and the level of mRNA encoding prodynorphin in the striatum on the lesioned side were decreased compared with the contralateral control side. Activation of DA receptors by 7 daily injections of APO (5 mg/kg, Bid, s.c.), however, caused a large increase (3- to 4-fold of saline control) in striatal levels of DN-LI and prodynorphin mRNA on the 6-OHDA lesioned side, which is far greater than the increase on the contralateral side (2-fold of saline control). Presumably, the potentiated effect of APO in 6-OHDA lesioned rats is due to hypersensitivity of DA receptors resulting from DA denervation. Seven daily injections of AMP (5 mg/kg, Bid, s.c.), a DA-releasing agent, increased striatal DN-LI (187% of saline control) on the non-lesioned side, but not on the 6-OHDA-lesioned side. Taken together, the data indicate that the nigrostriatal pathway exerts a tonic excitatory influence over the biosynthesis of dynorphin and that this influence is not maximal since an additional increase in dopaminergic tone further increases the expression of dynorphin. In contrast, [Met5]-enkephalin-like immunoreactivity (ME-LI) in the striatum was increased by a 6-OHDA-lesion (145% of contralateral control), which was blocked by repeated administration of APO but not AMP.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Apomorfina/farmacologia , Corpo Estriado/fisiologia , Dextroanfetamina/farmacologia , Dopamina/fisiologia , Dinorfinas/biossíntese , Encefalinas/biossíntese , Substância Negra/fisiologia , Animais , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Dinorfinas/genética , Hidroxidopaminas/farmacologia , Masculino , Oxidopamina , RNA Mensageiro/análise , RNA Mensageiro/genética , Ratos , Ratos Endogâmicos F344 , Valores de Referência , Substância Negra/efeitos dos fármacosRESUMO
The effects of single or repeated electroconvulsive shocks (ECS) on the abundance of mRNAs coding for prodynorphin (DYN mRNA) and proenkephalin (EK mRNA) in rat brain were investigated. Rats were given either a single ECS and sacrificed at 0.5, 2, 6, or 12 h post-shock (expt. I), or were subjected to ECS for 1, 3 or 6 days and killed 24 h after the last shock (expt. II). The amounts of DYN mRNA and EK mRNA were measured in several brain regions using RNA blot analysis. In expt. I, a biphasic change in the DYN mRNA level was found in the hippocampus, with an initial 49% decrease at 0.5 h followed by a 51% increase at 6 h after a single ECS. The EK mRNA content in the entorhinal cortex started to increase at 0.5 h, and continued to rise, reaching 260% of the control level at 12 h post-shock. A smaller increase in the EK mRNA level was found also in the hippocampus at 2 to 12 h post-shock. No significant increase in [Met5]-enkephalin or dynorphin A(1-8) immunoreactivity was detected by radioimmunoassay in either area. In expt. II, a dramatic reduction in the DYN mRNA level was observed in the hippocampus 24 h after a single or repeated ECS. In contrast, elevated DYN mRNA levels were seen in the striatum and hypothalamus. The EK mRNA level remained elevated in the entorhinal cortex after 6 daily ECS.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Encéfalo/metabolismo , Eletrochoque , Encefalinas/metabolismo , Regulação da Expressão Gênica , Precursores de Proteínas/metabolismo , RNA Mensageiro/metabolismo , Animais , Encefalinas/genética , Imuno-Histoquímica , Masculino , Precursores de Proteínas/genética , RNA Mensageiro/genética , Ratos , Ratos Endogâmicos F344RESUMO
Radioimmunoassay revealed increased dynorphin A(1-8)-like immunoreactivity [dynA(1-8)LI] in the aged rat brain. Among a number of brain regions examined, an age-related dynA(1-8)LI elevation was found only in the hippocampal formation and frontal cortex. Moreover, the increase in dynA(1-8)LI in the aged hippocampus was associated with a decline in spatial learning ability: dynA(1-8)LI distinguished aged rats that were behaviorally impaired from aged cohorts that learned the spatial task as rapidly as younger animals. Northern blot hybridization using a 32P-labeled complementary RNA probe encoding rat prodynorphin indicated that the abundance of prodynorphin mRNA was also significantly increased in the hippocampal formation of aged rats with identified spatial learning impairments.