Department of Psychology and Neuropsychology Doctoral Sub-Program Queens College, City University of New York, Flushing, New York, USA.
Int J Neurosci. 2010 Apr;120(4):265-72. doi: 10.3109/00207451003662120.
Male rodents displayed greater magnitudes of analgesia following systemic, ventricular, and intracerebral administration of mu-opioid receptor agonists than female rodents. Whereas neonatal castration of male rat pups produced reductions in systemic and central morphine analgesia as adults, neonatal androgenization of female rat pups treated with testosterone propionate (TP) displayed enhancements in systemic and central morphine analgesia as adults. Adult gonadectomy minimally affected mu-opioid analgesia, except if less potent mu agonists were employed, or if morphine was directly administered into the ventrolateral periaqueductal gray (vlPAG). Adult ovariectomy failed to appreciably alter the enhanced analgesia following systemic morphine in female rats with neonatal androgenization. Because the vlPAG elicited morphine analgesia that was sensitive to both neonatal and adult gonadal hormone manipulations, the present study examined morphine analgesia elicited from the vlPAG in female rats receiving neonatal treatment with TP or vehicle and subsequently exposed to adult ovariectomy or sham surgery as well as intact male rats. Intact male rats displayed significantly greater magnitudes and potencies in vlPAG morphine analgesia than female rats receiving neonatal treatment with either vehicle or TP. In turn, neonatal androgenization significantly enhanced vlPAG morphine analgesia relative to neonatal vehicle treatment in females. Adult ovariectomy significantly enhanced the magnitude of vlPAG morphine analgesia in female rats receiving neonatal treatment with either vehicle or TP. This demonstrates a strong interaction between neonatal and adult gonadal hormone manipulations in the mediation of vlPAG morphine analgesia in female rats.
雄性啮齿动物在全身、脑室和脑内给予μ-阿片受体激动剂后表现出比雌性啮齿动物更大程度的镇痛作用。然而，雄性幼鼠的新生阉割导致成年后全身和中枢吗啡镇痛作用降低，而用丙酸睾酮（TP）处理的雌性幼鼠的新生雄激素化则显示成年后全身和中枢吗啡镇痛作用增强。成年性腺切除术对μ-阿片类镇痛的影响很小，除非使用较弱的μ激动剂，或者吗啡直接注入腹外侧导水管周围灰质（vlPAG）。成年卵巢切除术未能明显改变新生雄激素化雌性大鼠全身吗啡后增强的镇痛作用。由于 vlPAG 诱发的吗啡镇痛作用对新生和成年性腺激素处理均敏感，因此本研究在接受新生 TP 或载体处理的雌性大鼠中检查了 vlPAG 中吗啡镇痛作用，然后暴露于成年卵巢切除术或假手术以及完整雄性大鼠。与接受新生处理的载体或 TP 的雌性大鼠相比，完整雄性大鼠在 vlPAG 吗啡镇痛中表现出显著更大的幅度和效力。反过来，新生雄激素化与新生载体处理的雌性大鼠相比，显著增强了 vlPAG 吗啡镇痛作用。成年卵巢切除术显著增强了接受新生处理的载体或 TP 的雌性大鼠 vlPAG 吗啡镇痛的幅度。这表明在介导雌性大鼠 vlPAG 吗啡镇痛作用中，新生和成年性腺激素处理之间存在强烈的相互作用。
