Sex chromosome complement affects nociception in tests of acute and chronic exposure to morphine in mice - PubMed (original) (raw)

Comparative Study

Sex chromosome complement affects nociception in tests of acute and chronic exposure to morphine in mice

Laura Gioiosa et al. Horm Behav. 2008 Jan.

Abstract

We tested the role of sex chromosome complement and gonadal hormones in sex differences in several different paradigms measuring nociception and opioid analgesia using "four core genotypes" C57BL/6J mice. The genotypes include XX and XY gonadal males, and XX and XY gonadal females. Adult mice were gonadectomized and tested 3-4 weeks later, so that differences between sexes (mice with testes vs. ovaries) were attributable mainly to organizational effects of gonadal hormones, whereas differences between XX and XY mice were attributable to their complement of sex chromosomes. In Experiment 1 (hotplate test of acute morphine analgesia), XX mice of both gonadal sexes had significantly shorter hotplate baseline latencies prior to morphine than XY mice. In Experiment 2 (test of development of tolerance to morphine), mice were injected twice daily with 10 mg/kg morphine or saline for 6 days. Saline or the competitive NMDA antagonist CPP (3-(2-carboxypiperazin-4yl) propyl-1-phosphonic acid) (10 mg/kg) was co-injected. On day 7, mice were tested for hotplate latencies before and after administration of a challenge dose of morphine (10 mg/kg). XX mice showed shorter hotplate latencies than XY mice at baseline, and the XX-XY difference was greater following morphine. In Experiment 3, mice were injected with morphine (10 mg/kg) or saline, 15 min before intraplantar injection of formalin (5%/25 microl). XX mice licked their hindpaw more than XY mice within 5 min of formalin injection. The results indicate that X- or Y-linked genes have direct effects, not mediated by gonadal secretions, on sex differences in two different types of acute nociception.

PubMed Disclaimer

Figures

Figure 1

Hotplate latencies in experiment 1, in gonadectomized experimentally naïve mice prior to injection of morphine. XX mice showed significantly shorter latencies than XY mice, irrespective of the type of gonad (asterisk, p<0.00001).

Figure 2

A, Hotplate latencies of XX mice were consistently shorter than those for XY mice prior to and after injection of the challenge dose of morphine in experiment 2 (asterisk, p<0.00001). To illustrate the sex chromosome effect clearly, the graphs show XX and XY groups collapsed across drug conditions. The XX-XY difference was larger 30–90 minutes after the injection of morphine on day 7 than prior to injection (time 0). B, Hotplate latencies of drug groups in experiment 2. The groups are collapsed across sex and sex chromosome conditions so that the overall drug effects can be observed more clearly. Morphine treatment on days 1–6 induced tolerance (shorter latencies) in response to morphine on day 7 (SAL-MOR shorter latencies than SAL-SAL, asterisk, p=0.01), but CPP did not affect morphine tolerance (no statistically significant difference between CPP-MOR and SAL-MOR).

Figure 3

A, Number of seconds spent licking in the first five minutes of the formalin test in experiment 3, collapsed across drug treatment groups. XX mice showed significantly more licking that XY mice (asterisk, p=0.03). B, The number of seconds spent licking in each of 10 5-minute intervals in experiment 3, collapsed across sex and sex chromosome groups because of the absence of sex or sex chromosome effects. The saline-injected mice showed the acute phase of licking for about five minutes, followed by a persistent pain phase during the last eight time segments. Morphine abolished all licking.

References

1. Agate RJ, Grisham W, Wade J, Mann S, Wingfield J, Schanen C, Palotie A, Arnold AP. Neural not gonadal origin of brain sex differences in a gynandromorphic finch. Proc. Natl. Acad. Sci. USA. 2003;100:4873–4878. - PMC - PubMed
1. Arnold AP. Concepts of genetic and hormonal induction of vertebrate sexual differentiation in the twentieth century, with special reference to the brain. In: Pfaff DW, Arnold AP, Etgen A, Fahrbach S, Rubin R, editors. Hormones, Brain, and Behavior. Vol. 4. San Diego: Academic Press; 2002. pp. 105–135.
1. Arnold AP, Burgoyne PS. Are XX and XY brain cells intrinsically different? TrendsEndocrinol. Metabol. 2004;15:6–11. - PubMed
1. Barrett AC, Cook CD, Terner JM, Craft RM, Picker MJ. Importance of sex and relative efficacy at the mu opioid receptor in the development of tolerance and cross-tolerance to the antinociceptive effects of opioids. Psychopharmacology (Berl) 2001;158:154–164. - PubMed
1. Berkley KJ. Sex differences in pain. Behav. Brain Sci. 1997;20:371-+. - PubMed

Sex chromosome complement affects nociception in tests of acute and chronic exposure to morphine in mice - PubMed (original) (raw)