Roles of prostaglandins D_2 and E_2 in the site of action for their sleep-wake regulation

前列腺素（PG） d2的促睡眠作用位点位于睡眠中枢视前区；然而，我们的实验结果表明，真正的作用部位位于位于视前区吻侧的基底前脑区域的腹面。基底前脑区包括腹侧纹状体，即伏隔核和嗅结节，以及布洛卡对角带和间隔区。我们还证明了该区域血流的变化与睡眠-觉醒状态的变化密切相关。脑PGD合成酶是脑内负责PGD_2合成的酶，在覆盖脑表面的轻脑膜中大量表达。大鼠脑脊液中PGD_2浓度在白天（动物睡眠期间）高于夜间。由此推测，在基底前脑吻侧腹面周围的膜组织中合成的PGD_2在脑区表层起促睡作用。PGD_2产生的信号可能被传递到负责睡眠-觉醒调节的神经回路。在这一过程中，腹侧纹状体中大量表达的A_<2a>-腺苷受体至关重要，因为A_<2a>-腺苷激动剂CGS21680能显著促进睡眠，而a_2 -腺苷拮抗剂KF17837则抑制PGD_2产生的睡眠促进作用。包括腹侧纹状体在内的这一区域可能是调节睡眠-觉醒的体液和神经元机制之间的界面结构。

The site of action for the sleep-promoting effect of prostaglandin (PG) D_2 had been postulated to be located in the preoptic area, a sleep center ; however, our experimental results showed that the real site of action is located in the ventral surface of a basal-forebrain region located rostral to the preoptic area. This basal-forebrain region includes ventral striatum, i.e., the accumbens nucleus and the olfactory tubercle, as well as the diagonal band of Broca and the septal region. We also demonstrated that changes in the regional blood flow in this area are closely correlated with the changes in the sleep-wake state. The brain PGD synthase, the enzyme responsible for the synthesis of PGD_2 in the brain, was shown to be abundantly expressed in the leptomeninges covering the surface of the brain. The concentration of PGD_2 in the cerebrospinal fluid (CSF) of the rat was higher during the daytime, the sleeping period of the animal, than during the night. Thus, it is postulated that PGD_2 synthesized in the membrane tissues surrounding the ventral surface of the rostral basal forebrain acts at the surface layr of the brain region to initiate sleep. The signal produced by PGD_2 may be transmitted to neural circuits responsible for the sleep-wake regulation. In the process, A_<2a>-adenosine receptors abundantly expressed in the ventral striatum are crucially involved, because CGS21680, an A_<2a>-adenosine agonist, markedly promoted sleep when administered to the same region, whereas KF17837, an A_2-adenosine antagonist, inhibited the sleep promotion produced by PGD_2. The region including the ventral striatum may serve as an interface structure between, humoral and neuronal mechanisms for the sleep-wake regulation.