Sex differences in locomotor effects of morphine in the rat

Abstract

Sex differences in reinforcing, analgesic and other effects of opioids have been demonstrated; however, the extent to which sex differences in motoric effects of opioids contribute to apparent sex differences in their primary effects is not known. The goal of this study was to compare the effects of the prototypic mu opioid agonist morphine on locomotor activity in male vs. female rats. Saline or morphine (1-10 mg/kg) was administered s.c. to adult Sprague-Dawley rats, which were placed into a photobeam apparatus for 3-5 h to measure activity. Modulation of morphine's effects by gonadal hormones and by handling (either during the test session or for 4 days before the test session) were examined. Morphine initially suppressed and later increased locomotor activity in both sexes relative to their saline-injected controls, but males were more sensitive than females to the initial locomotor suppressant effect of morphine. Intermittent, brief handling during the 3-h test session blunted morphine-induced locomotor activation in both sexes. Females in proestrus were the most sensitive to morphine's locomotor-stimulant effect, with females in estrus showing the least response to morphine. Gonadectomized (GDX) males with or without testosterone were equally sensitive to morphine's effects, whereas GDX females treated with estradiol showed a blunted response to morphine's effects, similar to intact females in estrus. Brief handling on each of 4 consecutive days pre-test attenuated morphine's locomotor suppressant effect in males but had no effect in females, thereby eliminating the sex difference. These data suggest that sex differences in morphine's effects on locomotor activity can be attributed to gonadal hormones in females, and to differential stress-induced modulation of morphine's effects in males vs. females.

Analysis of inflammation-induced depression of home cage wheel running in rats reveals the difference between opioid antinociception and restoration of function

“…As has been reported previously, both the antinociceptive and side effects of morphine tended to be greater in male compared to female rats [8,19]. This sex difference is apparent in the present study as low doses of morphine restored pain-depressed wheel running to a greater extent in male than female rats.…”

Some determinants of morphine effects on intracranial self-stimulation in rats

“…The biphasic time course of acute morphine effects on rates of ICSS is similar to the biphasic time course of morphine effects on rates of locomotor activity in rats (Vasko and Domino, 1978; Craft et al, 2006). For example, morphine (1–10 mg/kg sc) produced initial dose-dependent decreases (approximately 30–90 min post injection) followed by later increases (approximately 2–5 h post injection) in horizontal activity in male rats relative to their saline-treated controls (Craft et al, 2006).…”

Antagonism of mGlu2/3 receptors in the nucleus accumbens prevents oxytocin from reducing cued methamphetamine seeking in male and female rats

“…We have previously reported increased inactive lever responding in females relative to males using a limited access protocol (Reichel et al, 2012). Male and female rats exhibited discrimination between active and inactive response patterns so we attribute this finding to greater general activity of female rats relative males (Zhou et al, 2015; Craft et al, 2006; Caldarone et al, 2008; Wooters et al, 2006) and greater locomotor responses to stimulant drugs (Caldarone et al, 2008; Wooters et al, 2006). …”