Byrnes Elizabeth M, Bridges Robert S, Scanlan Victoria F, Babb Jessica A, Byrnes John J
Department of Biomedical Sciences, Tufts University Cummings School of Veterinary Medicine, North Grafton, MA 01536, USA.
Neuropsychopharmacology. 2007 May;32(5):1021-31. doi: 10.1038/sj.npp.1301222. Epub 2006 Oct 18.
There is much speculation regarding the effects of estrogen withdrawal at the end of pregnancy on forebrain dopamine, however, few studies have directly examine changes in this system postpartum. The present work sought to determine what changes in forebrain dopamine function occur in the postpartum rat. Specifically, prepulse inhibition of the acoustic startle response (PPI) was measured in primiparous female rats on postpartum day 2 (PPD2) or 14 (PPD14) following treatment with saline or the dopamine D2 agonist, quinpirole. Diestrus (DI) females served as controls. Dopamine content and turnover as well as cyclic AMP (cAMP) accumulation were determined within the nucleus accumbens and dorsal striatum in these same females. In addition, circulating levels of plasma corticosterone, estradiol and progesterone were measured. PPI was significantly disrupted in both postpartum groups. This effect was associated with decreased cAMP content within the nucleus accumbens. Quinpirole treatment (0.1 and 0.5 mg/kg) dose-dependently disrupted PPI in DI controls while PPD2 and PPD14 animals demonstrated reduced sensitivity to the D2 agonist. PPD14 animals demonstrated increased startle amplitude, an effect that was attenuated by quinpirole treatment. PPD14 females were also less sensitive to quinpirole-mediated reductions in DA turnover within the nucleus accumbens and both PPD2 and PPD14 females had an attenuated response to the stimulatory effects of quinpirole on corticosterone secretion. Collectively these findings suggest that the postpartum period is associated with reduced sensorimotor gating and altered forebrain DA systems, which may be related to shifts in circulating hormones.
关于妊娠末期雌激素撤退对前脑多巴胺的影响存在诸多猜测，然而，很少有研究直接考察产后该系统的变化。本研究旨在确定产后大鼠前脑多巴胺功能会发生哪些变化。具体而言，在初产雌性大鼠产后第2天（PPD2）或第14天（PPD14），用生理盐水或多巴胺D2激动剂喹吡罗处理后，测量其听觉惊吓反应的前脉冲抑制（PPI）。处于动情间期（DI）的雌性大鼠作为对照。测定这些相同雌性大鼠伏隔核和背侧纹状体内的多巴胺含量、周转率以及环磷酸腺苷（cAMP）积累。此外，测量血浆皮质酮、雌二醇和孕酮的循环水平。两个产后组的PPI均显著受损。这种效应与伏隔核内cAMP含量降低有关。喹吡罗处理（0.1和0.5mg/kg）在DI对照组中剂量依赖性地破坏PPI，而PPD2和PPD14组动物对D2激动剂的敏感性降低。PPD14组动物的惊吓幅度增加，喹吡罗处理可减弱这种效应。PPD14雌性大鼠对喹吡罗介导的伏隔核内多巴胺周转率降低也较不敏感，并且PPD2和PPD14雌性大鼠对喹吡罗对皮质酮分泌的刺激作用的反应均减弱。这些研究结果共同表明，产后时期与感觉运动门控降低和前脑多巴胺系统改变有关，这可能与循环激素的变化有关。
