Sex hormone levels and expression of their receptors in lactating and lactating pregnant rats.

Parturient rats show a postpartum estrus, a period of sexual receptivity that occurs from 6 to 15 h after the birth of a litter, which allows the mother to gestate a second litter while simultaneously nursing the first one (lactating and pregnant). The present study investigated hormone levels and the expression pattern of estrogen receptor α, and ß, progesterone receptor isoforms and SRC1 in the hypothalamus and the preoptic area of lactating as well as in lactating-pregnant rats. In the latter, estradiol levels were 3-fold higher than those observed in lactating rats on day 14, meanwhile progesterone levels did not change in any condition. There were higher levels of prolactin in both lactating and lactating-pregnant rats on day 7 and decreased on the following days. In the hypothalamus of the lactating rat, the content of ERα increased during lactation meanwhile that of ERß decreased 50% on day 10. The content of both estrogen receptor subtypes in the hypothalamus increased 3-fold on day 21 in lactating-pregnant rats. In the preoptic area, the content of ERα was higher in lactating-pregnant rats on days 14 and 21 while the content of progesterone receptor isoforms was lower as compared with those found in lactating animals on days 7 and 10. The content of SRC1 increased 2-fold in the preoptic area only in lactating rats at day 14 and 21. These findings suggest that lactating- pregnant animals should exhibit differential neuroendocrine and molecular characteristics as compared to lactating animals.

Sex hormones and expression pattern of cytoskeletal proteins in the rat brain throughout pregnancy.

Pregnancy involves diverse changes in brain function that implicate a re-organization in neuronal cytoskeleton. In this physiological state, the brain is in contact with several hormones that it has never been exposed, as well as with very high levels of hormones that the brain has been in touch throughout life. Among the latter hormones are progesterone and estradiol which regulate several brain functions, including learning, memory, neuroprotection, and the display of sexual and maternal behavior. These functions involve changes in the structure and organization of neurons and glial cells that require the participation of cytoskeletal proteins whose expression and activity is regulated by estradiol and progesterone. We have found that the expression pattern of Microtubule Associated Protein 2, Tau, and Glial Fibrillary Acidic Protein changes in a tissue-specific manner in the brain of the rat throughout gestation and the start of lactation, suggesting that these proteins participate in the plastic changes observed in the brain during pregnancy. This article is part of a Special Issue entitled 'Pregnancy and Steroids'.

The Edinger-Westphal-lateral septum urocortin pathway and its relationship to alcohol consumption.

Identifying and characterizing brain regions regulating alcohol consumption is beneficial for understanding the mechanisms of alcoholism. To this aim, we first identified brain regions changing in expression of the inducible transcription factor c-Fos in the alcohol-preferring C57BL/6J (B6) and alcohol-avoiding DBA/2J (D2) mice after ethanol consumption. Drinking a 5% ethanol/10% sucrose solution in a 30 min limited access procedure led to induction of c-Fos immunoreactivity in urocortin (Ucn)-positive cells of the Edinger-Westphal nucleus (EW), suppression of c-Fos immunoreactivity in the dorsal portion of the lateral septum (LS) of both strains of mice, and strain-specific suppression in the intermediate portion of the LS and the CA3 hippocampal region. Because the EW sends Ucn projections to the LS, and B6 and D2 mice differ dramatically in EW Ucn expression, we further analyzed the Ucn EW-LS pathway using several genetic approaches. We find that D2 mice have higher numbers of Ucn-immunoreactive processes than B6 mice in the LS and that consumption of ethanol/sucrose in the F2 offspring of a B6D2 intercross positively correlates with Ucn immunoreactivity in the EW and negatively correlates with Ucn immunoreactivity in the LS. In agreement with these findings, we find that alcohol-avoiding male B6.D2 Alcp1 line 2.2 congenic mice have lower Ucn immunoreactivity in the EW than male B6.B6 mice. Finally, we also find that HAP mice, selectively bred for high alcohol preference, have higher Ucn immunoreactivity in EW, than LAP mice, selectively bred for low alcohol preference. Taken together, these studies provide substantial evidence for involvement of the EW-LS Ucn pathway in alcohol consumption.

High alcohol/sucrose consumption during dark circadian phase in C57BL/6J mice: involvement of hippocampus, lateral septum and urocortin-positive cells of the Edinger-Westphal nucleus.

RATIONALE: Identification of the neuroanatomical substrates regulating alcohol consumption is important for the understanding of alcoholism. Previous studies mapping changes in brain activity used rodent models of alcohol drinking with relatively low alcohol intakes. OBJECTIVES: This study was aimed to identify brain regions changing activity after high voluntary intake of alcohol-containing solutions. METHODS: Adult male C57BL/6J mice were trained to drink a 10% ethanol/10% sucrose solution in daily 30-min limited-access sessions during the dark phase of the circadian cycle. Control groups of animals consumed 10% sucrose or water. Analysis of c-Fos immunohistochemistry (as a marker for neuronal activity) was performed at 90 min after the last alcohol drinking session. RESULTS: The limited access procedure led to high intakes (2.9+/-0.3 g/kg) and blood alcohol concentrations of 251+/-46 mg%. Expression of c-Fos was significantly higher in the alcohol/sucrose group than both the water and sucrose groups in the Edinger-Westphal nucleus, and significantly lower in the alcohol/sucrose group than two control groups in hippocampal subregions, posterior hypothalamus and dorsal lateral septum. Double immunohistochemistry showed that alcohol-induced c-Fos-positive cells in the Edinger-Westphal nucleus co-localized with the neuropeptide urocortin. In addition, intake and/or blood alcohol concentrations correlated with c-Fos expression in specific subregions of the hippocampus, hypothalamus, prefrontal cortex, lateral septum and midbrain. CONCLUSIONS: The dark phase voluntary limited-access procedure in mice leads to intakes of alcohol-containing solutions that are considered highly intoxicating. Brain regions showing alcohol-specific changes in c-Fos expression after this procedure can be connected into a novel neurocircuit, including lateral septum, hippocampus, hypothalamus, and the Edinger-Westphal nucleus.