Journal of neuroscience research
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The mechanisms of hypertension-induced hypoalgesia were studied in a model of hypertension induced by adenosine receptors blockade with the non-selective antagonist 1,3-dipropyl-8-sulfophenylxanthine (DPSPX) during 7 days. Based on the positive correlation between pain thresholds and noxious-evoked expression of the c-fos protooncogene in spinal cord neurones, we used this marker of nociceptive activation of spinal neurones to evaluate the involvement of the spinal GABAergic system and the caudal ventrolateral medulla (VLM), an important inhibitory component of the supraspinal endogenous pain modulatory system. In DPSPX-treated animals, a 20% increase in blood pressure was achieved along with a decrease in Fos expression in the superficial (laminae I-II) and deep (laminae III-VII) dorsal horn. ⋯ Lesioning the VLMlat with quinolinic acid prevented the decrease in Fos expression at the spinal cord of DPSPX-hypertensive rats whereas in normotensive animals, no changes in Fos expression were detected. The present results support previous findings that hypertension is associated with a decrease of nociceptive activation of spinal cord neurones, through descending inhibition exerted by the VLMlat. This study further shows that during hypertension a decrease in the expression of GABAB receptors in nociceptive spinal neurones occurs, probably due to changes in the local GABAergic inhibitory system.
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The nucleus accumbens (NAcc) and central amygdala (CeA) are parts of the extended amygdala, a complex that plays a key role in drug abuse and dependence. Our previous studies showed that opiates and ethanol alter glutamatergic transmission in these regions. N-methyl-D-aspartate (NMDA) receptors are key components of glutamatergic transmission likely involved in the development of opiate tolerance and dependence. ⋯ In contrast to the case for NAcc, in CeA we found an increased mRNA level for the NR1 subunit only but unchanged protein levels of all three subunits in morphine-dependent rats. The altered expressions of NMDA receptor subunits, especially in NAcc, of morphine-dependent rats may represent a neuroadaptation to chronic morphine and suggest a mechanism for the changes of glutamatergic transmission found in the extended amygdala in dependent rats. In addition, our results indicate a region-specific response of NMDA receptor subunits to chronic morphine administration at the gene and protein levels.