Figure 2: Administrations of estrogens (E2 and/or EE) and DHED reduce naloxone-induced TST rise in morphine-dependent OVX rats. Orally administered DHED also restores rhythmic oscillation of TST in OVX rats.
(a) The effect of s.c. treatments on TST. Left side: TST starts to elevate 5 min after naloxone treatment and reaches peak values between 10–15 min, after which TST drops and eventually returns to baseline by 60 min (not shown). While naloxone withdrawal induces a 5 °C increase in TST of OVX-vehicle-treated rats (black trace), E2 (red trace), EE (magenta trace) and DHED (green trace) blunt this rise to less than 2 °C. Chart on the right: TST values measured at 15 min after naloxone injection (arrow). All three treatments blunted TST rise compared to OVX-vehicle-treated animals. Data represent mean ± SEM. *P < 0.01 compared with vehicle-treated OVX group. (b) The effects of orally administered DHED (10, 30 or 100 μg/kg), EE (200 μg/kg), or vehicle on the mean changes in TST. Both DHED (shades of green, increasing dose reflected by darker color) and EE (magenta) blunt TST rise compared to OVX-vehicle-treated animals (black). Data represent mean ± SEM. *P < 0.05 compared with vehicle-treated OVX group. (c) The effect of DHED administered orally (50 μg/kg b.i.d.) on diurnal TST changes. The TST of intact animals (blue line) show rhythmic changes during the active and passive phases of the day. The TST of OVX rats (red line) does not show diurnal changes. However, when OVX rats are treated with DHED from day 5 through 9, the diurnal changes return to those seen in intact rats. When DHED treatment is terminated on day 10, the undulating TST changes disappear.
