It is well known that the dopamine D
3 receptor plays a critical role in several psychological disorders, such as drug dependence. The present study was designed to investigate the influence of ...lacking dopamine D
3 receptors in dopamine-induced G-protein activation and Ca
2+ influx in the mouse forebrain. The deletion of dopamine D
3 receptor gene caused the enhancement of dopamine-induced G-protein activation in the limbic forebrain of dopamine D
3 receptor knockout (D
3KO) mice. Furthermore, the dopamine-induced Ca
2+ influx was enhanced in the coculture of neuron/glia cells obtained from the forebrain of D
3KO mice. The present data provide direct evidence that a deletion of central dopamine D
3 receptor enhances the dopamine D
1/D
2 receptor-mediated intracellular signaling.
It has been widely recognized that chronic pain could cause physiological changes at supraspinal levels. The delta-opioidergic system is involved in antinociception, emotionality, immune response and ...neuron-glia communication. In this study, we show that mice with chronic pain exhibit anxiety-like behavior and an increase of astrocytes in the cingulate cortex due to the dysfunction of cortical delta-opioid receptor systems. Using neural stem cells cultured from the mouse embryonic forebrain, astrocyte differentiation was clearly observed following long-term exposure to the selective delta-opioid receptor antagonist, naltrindole. We also found that micro-injection of either activated astrocyte or astrocyte-conditioned medium into the cingulate cortex of mice aggravated the expression of anxiety-like behavior. Our results indicate that the chronic pain process promotes astrogliosis in the cingulate cortex through the dysfunction of cortical delta-opioid receptors. This phenomenon may lead to emotional disorders including aggravated anxiety under chronic pain-like state. PUBLICATION ABSTRACT
The present study was designed to examine the change in astrocyte during the development of sensitization to methamphetamine (METH) in the rodent. Here we found that in vitro treatment with METH into ...the cortical neuron/glia cocultures for 3 days caused the activation of astrocytes, as detected by a stellate morphology and an increase in glial fibrillary acid protein (GFAP). These effects were reversed by coculture with the specific protein kinase C (PKC) inhibitor chelerythrine, suggesting that PKC may be implicated in these events. Furthermore, the levels of GFAP immunoreactivity in the cingulate cortex and nucleus accumbens of mice were clearly increased by repeated in vivo treatment with METH, which produced behavioral sensitization. The development of behavioral sensitization to METH associated with the increased astrocyte was completely blocked by co-treatment with the PKC inhibitor NPC-15437. These results lead to direct evidence for the development of METH-induced behavioral sensitization through the stimulation of astrocytic PKC.
Two-way communication between neurons and glial cells is considered to be essential for axonal conduction and synaptic transmission. Here we found that the levels of glial fibrillary acidic protein ...(GFAP), a specific astrocyte marker, in the cingulated gyrus and nucleus accumbens of mice were clearly increased by repeated in vivo treatment with methamphetamine (METH) which was associated with behavioral sensitization. Furthermore, the dramatic increase of reactive astrocytes in the dorsal horn of the spinal cord was clearly observed by repeated treatment with morphine (MRP). These effects were reversed by the specific protein kinase C (PKC) inhibitor, suggesting that PKC may be implicated in these events. In contrast, there was no change in microglia. These results constitute direct evidence for the astrocytic activation induced by chronic treatment with METH and MRP. Such findings raise the fascinating possibility that the astrocytic response is involved in the development of METH- and MRP-induced neuronal plasticity in the mammalian central nervous system.
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