Sex-specific differences in pain response by dopamine in the bed nucleus of the stria terminalis in rats

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Abstract

The formalin test for nociception shows characteristic sex differences in the pain response during the interphase period of the test. However, the mechanism underlying these differences remains unclear. We have recently reported the sex-specific involvement of the lateral subdivision of the bed nucleus of the stria terminalis (BSTL) in the formalin test in rats. Here, we evaluated whether sex-specific differences in the pain response were modulated by the dopamine system in the BSTL. We first examined the effects of injecting a dopamine D1 receptor agonist, dihydrexidine, or antagonist, SCH23390, into the BSTL on the formalin test. During the interphase of the formalin test, injection of the D1 receptor agonist exerted no effect in male or female rats. The antagonist significantly enhanced the nociceptive response in female rats but not in males, indicating a sex difference in the involvement of the dopamine system in the formalin test. Next, we examined the expression of dopamine D1 receptors in the BSTL. Immunohistochemical analysis showed that the dopamine D1 receptor was expressed in the BSTL in both sexes but showed stronger immunoreactivity in male rats than in females. These results suggest sex-specific differences in the formalin test in which the response of dopamine neurons projecting to the BSTL plays a role in attenuating pain in female rats.

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