Helms Christa M, McCracken Aubrey D, Heichman Sharon L, Moschak Travis M
Oregon National Primate Research Center, Division of Neuroscience, Oregon Health & Science University, Beaverton, Oregon 97006-6448, USA.
Behav Pharmacol. 2013 Apr;24(2):95-104. doi: 10.1097/FBP.0b013e32835efc5f.
Past studies have suggested that progesterone-derived ovarian hormones contribute to the discriminative stimulus effects of ethanol, particularly via progesterone metabolites that act at γ-aminobutyric acid type A (GABA(A)) receptors. It is unknown whether loss of ovarian hormones in women, for example, after menopause, may be associated with altered receptor mediation of the effects of ethanol. The current study measured the substitution of allopregnanolone, pregnanolone, pentobarbital, midazolam, dizocilpine, TFMPP, and RU 24969 in female sham and ovariectomized rats trained to discriminate 1.0 g/kg ethanol from water. The groups did not differ in the substitution of GABA(A)-positive modulators (barbiturates, benzodiazepines, neuroactive steroids) or the N-methyl-D-aspartate receptor antagonist dizocilpine. Similarly, blood-ethanol concentration did not differ between the groups, and plasma adrenocorticotropic hormone, progesterone, pregnenolone, and deoxycorticosterone were unchanged 30 min after administration of 1.0 g/kg ethanol or water. However, substitution of neuroactive steroids and RU 24969, a 5-hydroxytryptamine (5-HT)(1A/1B) receptor agonist, was lower than observed in previous studies of male rats, and TFMPP substitution was decreased in ovariectomized rats. Ovarian hormones appear to contribute to 5-HT receptor mediation of the discriminative stimulus effects of ethanol in rats.
以往的研究表明，孕酮衍生的卵巢激素会导致乙醇的辨别刺激效应，尤其是通过作用于γ-氨基丁酸A型（GABA(A)）受体的孕酮代谢产物。例如，女性在绝经后卵巢激素的丧失是否可能与乙醇效应的受体介导改变有关尚不清楚。本研究测量了在经过训练以区分1.0 g/kg乙醇和水的雌性假手术大鼠和去卵巢大鼠中，别孕烷醇酮、孕烷醇酮、戊巴比妥、咪达唑仑、地佐环平、TFMPP和RU 24969的替代情况。两组在GABA(A)阳性调节剂（巴比妥类、苯二氮䓬类、神经活性甾体）或N-甲基-D-天冬氨酸受体拮抗剂地佐环平的替代方面没有差异。同样，两组之间的血液乙醇浓度没有差异，并且在给予1.0 g/kg乙醇或水30分钟后，血浆促肾上腺皮质激素、孕酮、孕烯醇酮和脱氧皮质酮没有变化。然而，神经活性甾体和5-羟色胺（5-HT）(1A/1B)受体激动剂RU 24969的替代低于先前对雄性大鼠的研究中观察到的情况，并且在去卵巢大鼠中TFMPP的替代减少。卵巢激素似乎有助于大鼠中乙醇辨别刺激效应的5-HT受体介导。
