Gonadal steroid hormone modulation of nociception, morphine antinociception and reproductive indices in male and female rats

Abstract

The purpose of this study was to examine how gonadal steroid hormones modulate basal nociception and morphine antinociception relative to regulating reproduction in the adult rat. Male and female Sprague-Dawley rats were either gonadectomized (GDX) or sham-gonadectomized (sham); GDX males were implanted subcutaneously with capsules containing testosterone (T), estradiol (E2), dihydrotestosterone (DHT), E2 and DHT, or nothing (0). GDX females received E2, T, or empty (0) capsules immediately after surgery, and vehicle or progesterone (P4) injections at 4-day intervals. Basal nociception and morphine antinociception were tested 28 days after surgery on 50 degrees C and 54 degrees C hotplate tests, and reproductive behavior and physiology were assessed shortly thereafter. There were no significant differences in baseline hotplate latencies among the male treatment groups, but morphine was significantly more potent in sham and GDX+T males than in GDX+0 males. The ability of T to increase morphine's potency was approximated by its major metabolites E2 and DHT, given together but not alone. Baseline hotplate latencies were higher in sham females tested during diestrus than in those tested during estrus. Morphine was significantly more potent in sham females tested during proestrus and diestrus than in those tested during estrus. Baseline hotplate latencies were significantly higher, and morphine was significantly less potent in GDX+E2, GDX+E2/P4 and GDX+T females than in GDX+0 females. All group differences in basal nociception and morphine antinociception observed on the 50 degrees C hotplate test were smaller and generally non-significant on the 54 degrees C hotplate test. Steroid manipulations produced the expected changes in reproductive behaviors and steroid-sensitive organs. These results demonstrate that in adult rats, gonadal steroid manipulations, that are physiologically relevant, modulate (1) basal nociception in females but not males, and (2) morphine's antinociceptive potency in both males and females.

Fig. 1

Males: effects of GDX and steroid hormone replacement on basal nociception on the 50°C hotplate test. Each bar is the mean + 1 SEM of seven to eleven rats. For treatment group abbreviations see Table 2; only high-dose T group is shown.

Fig. 2

Males: effects of GDX and steroid hormone replacement on morphine antinociception on the 50°C hotplate test. Each point is the mean ± 1 SEM of seven to eleven rats. For treatment group abbreviations see Table 2; only high dose T group is shown.

Fig. 3

Males: effects of GDX and steroid hormone replacement on reproductive behavior (top panel) and physiology (bottom panel). Top panel: copulatory rate = male reproductive behaviors (mounts, intromissions, ejaculation)/min; copulatory efficiency = number of intromissions and the ejaculation relative to total reproductive behaviors performed. Each bar is the mean + 1 SEM of seven to ten rats. Bottom panel: weight of steroid-sensitive organs; each bar is the mean + 1 SEM of five to 11 organs. For treatment group abbreviations see Table 2; only high dose T group is shown. *Significantly different from GDX + 0, P ≤ 0.05, Dunnett's.

Fig. 4

Intact females: effects of estrous stage on basal nociception on the 50°C hotplate test in sham-GDX females (D, diestrus-1; P, proestrus; E, estrus). Each bar is the mean + 1 SEM of seven to ten rats. *Significantly different from sham-D, P ≤ 0.05, Student–Newman–Keuls.

Fig. 5

Intact females: effects of estrous stage on morphine antinociception on the 50°C hotplate test in sham-GDX females (D, diestrus-1; P, proestrus; E, estrus). Each point is the mean ± 1 SEM of seven to eleven rats.

Fig. 6

Intact females: effects of estrous stage on reproductive behavior (top panel) and physiology (bottom panel) in sham-GDX females (D, diestrus-1; P, proestrus; E, estrus). Top panel: lordosis quotient, frequency of lordosis behavior shown by females when mounted by a male; each bar is the mean + 1 SEM of six to ten rats. Bottom panel: weight of the uterus, a steroid-sensitive organ; each bar is the mean + 1 SEM of six to eight organs. *Significantly different from sham-D, P ≤ 0.05, Student–Newman–Keuls.

Fig. 7

GDX females: effects of steroid hormone replacement on basal nociception on the 50°C hotplate test. Each bar is the mean + 1 SEM of eight to eleven rats. For treatment group abbreviations see Table 2; only low dose E2 group is shown. *Significantly different from GDX + 0, P < 0.05, Dunnett's.

Fig. 8

GDX females: effects of steroid hormone replacement on morphine antinociception on the 50°C hotplate test. Each point is the mean ± 1 SEM of eight to eleven rats. For treatment group abbreviations see Table 2; only low dose E2 group is shown.

Fig. 9

GDX females: effects of steroid hormone replacement on reproductive behavior (top panel) and physiology (bottom panel) in female rats. Top panel: lordosis quotient, the frequency of lordosis behavior shown by females when mounted by a male; each bar is the mean + 1 SEM of eight to eleven rats. Bottom panel: weight of the uterus, a steroid-sensitive organ; each bar is the mean + 1 SEM of eight to ten organs. For treatment group abbreviations see Table 2; only low dose E2 group is shown. *Significantly different from GDX + 0, P ≤ 0.05, Dunnett's.