Effect of Direct Application of Estrogen Aimed at Lateral Septum or Dorsal Raphe Nucleus on Lordosis Behavior: Regional and Sexual Differences in Rats

Abstract

The role of estrogen in lordosis-inhibiting systems in the lateral septum or the dorsal raphe nucleus was investigated in female and male rats. Ovariectomized rats received implantation of 22-gauge guide cannulae to the bilateral or right side of the lateral septum (LS and rLS, respectively), the dorsal raphe nucleus (DRN) or bilateral cortex (CX). In castrated male rats, bilateral implantations of the cannulae to the LS were carried out (mLS). Three behavioral tests in total were performed at 2-week intervals. In the first test, all animals were subcutaneously injected with 1.5 µg/kg estradiol benzoate (EB). Forty-four hours after EB, 0.5 mg progesterone (P) was injected and a behavioral test was started 4 h after P. These hormonal regimes were used in all tests. In the second test, 2 h before EB injection, 27-gauge cannulae filled with estradiol (E₂) were inserted into the DRN, LS or CX through the guide cannulae and were kept there for 4 h. In the third test, cholesterol was implanted instead of E₂ into these areas. In the first test, most females showed low levels of lordosis quotient (LQ) and most males showed no lordosis. In the second test, mean LQs in the LS or rLS groups of females increased but not in the DRN and CX groups. In the mLS group no increase of LQ was observed. When cholesterol was implanted in the third test, mean LQs in all groups were as low as in the first test. These results suggest the possibility that estrogen releases the inhibition when it acts on the LS, but not on the DRN female rats. On the other hand, inhibition in the male LS may not be released by the direct action of estrogen.

Effects of Highly or Relatively Selective 5-HT1AReceptor Agonists on Lordosis in Female Rats

“…5-HT 1A receptor function is influenced by estrogen (Jackson and Uphouse, 1998). On the other hand, estrogen does not seem to have a direct effect on the lordosis regulating function in the DRN, because direct application of the crystal estrogen into the DRN did not facilitate lordosis in subthreshold doses of estrogen-treated ovariectomized rats (Satou and Yamanouchi, 1999). Furthermore, it has been reported that the number of serotonin-immunopositive cells in the DRN is not influenced by estrogen (Lu et al, 2001).…”

Neonatal Estrogen Decreases Neural Density of the Septum–Midbrain Central Gray Connection Underlying the Lordosis-Inhibiting System in Female Rats

“…Sex difference in estrogen-dependent changes of synaptic number has been reported in the LS of adult rats [25]. Sensitivity of the LS neurons to estrogen shows a sex difference, because direct application of estrogen into the LS enhances lordosis in adult female rats but not in adult male rats [5]. It is probable that neonatal estrogen causes sexual differentiation of such estrogen-related mechanisms in the LS, although relationships between the sensitivity to estrogen and the density of the LS-MCG neural connections cannot be explained yet.…”

“…In contrast, the lateral septum (LS) exerts a lordosis-inhibiting influence, since lordosis is facilitated by either lesions of the LS [3]or transections of the output fibers of the LS [4]. This inhibitory influence can be counteracted by estrogen directly implanted into the LS [5]of ovariectomized rats. LS neurons, as well as VMH neurons, have been reported to send axons to the MCG [6, 7].…”

“…Surgically induced dysfunction of the LS causes male rats to display feminine sexual behavior [14, 15, 16]. In addition, direct application of estrogen into the LS does not facilitate lordosis in male rats, but does so in female rats [5]. …”

Effects of 5-HT1A-Receptor Agonist, 8-OH-DPAT, and GABAB-Receptor Agonist, Baclofen, on Lordosis in Female Rats With Lesions in Either the Dorsal Raphe Nucleus or Septum

“…Our previous report suggested that the role of the GABA B -receptor system in the DRN is dependent on the function of the serotonergic system in the DRN, because the inhibitory effect of baclofen on lordosis is attenuated by DRN lesions (1). However the mechanisms of inhibition in the DRN and the septum are thought to be different, because inhibition in the lateral septum, but not in the DRN is released by estrogen (22); moreover, inhibition in the DRN appears to be independent of that in the lateral septum (23).…”