ABSTRACT
Aim To explore the therapeutical effect and mechanism of baicalein on two 6-hydroxydopamine (6-OHDA ) induced Parkinson′s disease (PD ) rat models,which received unilateral lesions of the left medial forebrain bundle (MFB ) or caudate putamen (CPu ) made by stereotaxic injection of 6-OHDA (MFB-M,CPu-M).Methods PD rat models were established by microinjection of 6-OHDA into MFB or CPu.The anti-tremor effect of baicalein on PD rat models was examined.Spontaneous activity was recor-ded. Dopamine (DA ), dihydroxyphenylacetic acid (DOPAC)and homovanilic acid (HVA)in striatum were quantified by HPLC-ECD.The tyrosine hydroxy-lase (TH)and OX-42 positive cells were detected by immunohistochemical method.The morphological vari-ation of the neurons was confirmed by analysis at an ul-trastructural level.Results Baicalein significantly in-creased the spontaneous activity in CPu-M.The elec-tromyography (EMG ) recordings revealed that com-pared with 6-OHDA group,the tremor frequency in ba-icalein group was decreased by 55% in MFB-M,and by 60% in CPu-M.6-OHDA treatment decreased DA levels in the striatum,while treatment with baicalein attenuated the DA decreases in CPu-M.Moreover,ba-icalein treatment could increase TH-positive neurons and decrease OX-42-postive microglia compared with 6-OHDA group in both MFB-M and CPu-M.Conclu-sions In the present study,it is illustrated that ①microinjection of 6-OHDA into the MFB and the CPu could cause different pathological changes of PD, which is important for efficacy evaluation;②baicalein showed the ability to alleviate the behavior symptoms in PD-rats at different stages by improving motor function and attenuating muscle tremor;③therapeutic effect of baicalein was produced by inhibiting the inflammatory medium production and release,anti-apoptosis,chan-ging dopamine catabolism, and inhibiting dopamine turnover.
ABSTRACT
Biochemical and behavioral evidence indicates that the dopaminergic mesolimbic system plays a key role in the mechanisms of reinforcement and reward elicited by alcohol (ethanol) and other drugs of abuse. In addition, the dopaminergic activity of the nigrostriatal pathway has been proposed to determine brain sensitivity to ethanol, a process which could be associated to drug addiction. Besides dopamine, several neurotransmitters and neuromodulators are involved in ethanol reinforcement, including gamma aminobutyric acid (GABA), glutamate, serotonin, acetylcholine and opioid peptides (enkephalins, endorphins and dynorphins). Ethanol and opioids share several pharmacological properties and exhibit similar behavioral effects in animals and humans. These and other studies suggest that the alcohol reinforcing properties are due, at least in part, to the ethanol-induced activation of endogenous opioidergic systems. This activation could in turn increase the hedonic value and the reinforcing effects of the drug. Thus, ethanol-induced changes in opioidergic transmission could contribute to alcohol intoxication and to the neuroadaptive responses produced by the long-lasting exposure to the drug. Opioidergic transmission may be altered by ethanol at different levels, including biosynthesis, release and inactivation of opioid peptides, as well as binding of endogenous opioids to their receptors. Several studies suggest that mu and delta opioid receptors play a key role in ethanol reinforcement and dependence. Therefore, enkephalins and (β-endorphin could mediate ethanol actions in the brain and play a major role in high alcohol drinking behavior. During the last years, our research group has focused on the role of the endogenous opioid systems in these processes. Evidence obtained in our laboratory suggests that enkephalins and (β-endorphin differentially and selectively participate in ethanol reinforcement and dependence.
Evidencias bioquímicas y conductuales indican que el sistema dopaminérgico mesolímbico cumple un papel fundamental en los mecanismos de reforzamiento y recompensa del alcohol (etanol) y otras drogas de abuso. Se ha propuesto también que la actividad de la vía dopaminérgica nigroestriatal determina la sensibilidad cerebral a etanol, lo que parece estar directamente relacionado con los procesos de adicción a la droga. Además de la dopamina, varios neurotransmisores y neuromoduladores están implicados en los mecanismos de reforzamiento del etanol, entre ellos, el ácido gama-aminobutírico (GABA), el glutamato, la serotonina, la acetilcolina y los péptidos opioides (encefalinas, endorfinas y dinorfinas). El alcohol y los opioides comparten características farmacológicas y exhiben efectos similares sobre el comportamiento en animales y en el hombre. Éstos y otros estudios sugieren que las propiedades reforzadoras del etanol se deben, al menos parcialmente, a la activación de los sistemas endógenos de péptidos opioides, proceso que es inducido por el propio alcohol. Esta activación podría, a su vez, aumentar el valor hedónico y los efectos reforzadores de la droga. Los cambios inducidos por etanol sobre la transmisión de opioides podrían contribuir de manera importante a los procesos de intoxicación y a las respuestas neuronales adaptativas que produce el consumo prolongado de la droga. La transmisión opioidérgica puede ser afectada por etanol a distintos niveles, incluyendo la biosíntesis, liberación e inactivación de los opioides endógenos, así como la unión de éstos a sus receptores. Numerosas evidencias sugieren que los receptores opioides mu y delta desempeñan un papel fundamental en el reforzamiento y la dependencia al etanol. Así, las encefalinas y la (β-endorfina actuarían como mediadores fisiológicos de las acciones del etanol en el cerebro, desempeñando un papel crucial en las conductas de alto consumo de la droga. En los últimos años, nuestro grupo se ha centrado en investigar el papel de los sistemas endógenos de péptidos opioides en estos procesos. Las evidencias obtenidas en nuestro laboratorio sugieren que las encefalinas y la (β-endorfina participan en forma diferencial y selectiva en el reforzamiento y la dependencia al etanol.