Sex differences in NMDA antagonist enhancement of morphine antihyperalgesia in a capsaicin model of persistent pain: comparisons to two models of acute pain.

In acute pain models, N-methyl-D-aspartate (NMDA) antagonists enhance the antinociceptive effects of morphine to a greater extent in males than females. The purpose of this investigation was to extend these findings to a persistent pain model which could be distinguished from acute pain models on the basis of the nociceptive fibers activated, neurochemical substrates, and duration of the nociceptive stimulus. To this end, persistent hyperalgesia was induced by administration of capsaicin in the tail of gonadally intact F344 rats, following which the tail was immersed in a mildly noxious thermal stimulus, and tail-withdrawal latencies measured.

Sex differences in the potency of kappa opioids and mixed-action opioids administered systemically and at the site of inflammation against capsaicin-induced hyperalgesia in rats.

Rationale: Sex differences in the potency of the antinociceptive effects of kappa opioids have been reported in various acute pain models with evidence suggesting that these sex differences are mediated by activity in the N-methyl-D: -aspartate (NMDA) system.

Objectives: The purpose of the present study was to evaluate sex differences in the antihyperalgesic actions of selected kappa and mixed-action opioids in a persistent pain model and determine if the NMDA system modulates these effects in a sexually dimorphic manner.

Methods: Using gonadally intact male and female F344 rats, hyperalgesia was induced by local administration of capsaicin in the tail, after which the tail was immersed in a mildly noxious thermal stimulus (45 degrees C water), and tail-withdrawal latency measured.

Does stress reactivity or response to amphetamine predict smoking progression in young adults? A preliminary study.

Recent studies with laboratory animals indicate that a constellation of behavioral factors predict progression to self-administer drugs. Relatively little is known about behavioral or biological factors that predict the progression in drug use from initial experimentation to regular use in human drug users. The present exploratory study examined reactivity to an acute stressor and reactivity to a single dose of a dopaminergic drug as predictors in progression to heavier smoking in young cigarette smokers over a 6-month period.

Influence of low doses of naltrexone on morphine antinociception and morphine tolerance in male and female rats of four strains.

In a recently proposed bimodal opioid receptor model, the inhibitory actions of opioids on action potential duration in dorsal root ganglion neurons have been proposed to produce antinociception, and the excitatory actions of hyperalgesia. Recent studies indicate that selectively blocking these excitatory actions with low doses of opioid antagonists enhances opioid antinociception and attenuates the development of opioid tolerance. To determine if the excitatory actions of opioids contribute to sex as well as strain differences in opioid sensitivity, the effects of morphine alone and in combination with low doses of naltrexone were examined in male and female rats of four strains.

Menstrual cycle phase and responses to drugs of abuse in humans.

Researchers have recently become aware of the importance of including women in research, including drug abuse research. With this increased awareness has come an increased scientific interest in the potential influence of menstrual cycle phase on responses to drugs. In this review, we discuss recent studies that have examined subjective and physiological responses to drugs of abuse in relation to menstrual cycle phase.

Effects of the long-lasting kappa opioid 2-(3,4-dichlorophenyl)-N-methyl-N-[(1S)-1-(3-isothiocyanatophenyl)-2-(1-pyrrolidinyl) ethyl] acetamide in a drug discrimination and warm water tail-withdrawal procedure.

Although studies suggest that 2-(3,4-dichlorophenyl-N-methyl-N-[(1S)-1-(3-isothiocyanatophenyl)-2-(1-pyrrolidinyl) ethyl] acetamide (DIPPA) has transient kappa-opioid-mediated agonist effects followed by long-lasting kappa-antagonist effects, its behavioral and pharmacological actions have not been systematically examined and there is evidence suggesting that some of its effects are species dependent. The purpose of this investigation was to examine the actions of DIPPA in different behavioral procedures and in three species. In a pigeon drug discrimination procedure, DIPPA and the kappa-opioids U50,488 and ICI-199441 substituted fully for the stimulus effects produced by spiradoline.

Influence of estrous cycle and gonadal hormone depletion on nociception and opioid antinociception in female rats of four strains.

Unlabelled: Evidence suggests that gonadal hormones can modulate sensitivity to nociceptive stimuli and opioid antinociception. However, cross-study comparisons addressing the nature of this modulation have been complicated by a number of methodologic factors, including the use of different rodent strains and opioids. The present study examined the influence of estrous cycle and gonadal hormone depletion (ovariectomy) on thermal nociception and opioid antinociception in female F344, Lewis, Long Evans, and Wistar rats.

Pharmacogenetic analysis of sex differences in opioid antinociception in rats.

Sex differences in opioid antinociception have been reported in rodents and monkeys, with opioids being more potent in males than females. In the present study, the influence of rat strain on sex differences in opioid antinociception was examined in a warm water tail-withdrawal procedure. Antinociceptive tests were conducted with the high-efficacy micro-opioid morphine, and the less efficacious opioids buprenorphine, butorphanol and nalbuphine.

Influence of gonadectomy on the antinociceptive effects of opioids in male and female rats.

Rationale: Sex differences in the antinociceptive effects of opioids have been reported in a variety of nociceptive assays, and it has been postulated that these differences are mediated by gonadal hormones.

Objectives: The present study examined the influence of gonadectomy on opioid antinociception in male and female rats.

Methods: In a warm-water, tail-withdrawal procedure, the antinociceptive effects of the high-efficacy micro opioids etorphine and morphine; the low-efficacy micro opioids buprenorphine and dezocine; and the low-efficacy, mixed-action opioids butorphanol and nalbuphine were examined in intact and gonadectomized rats of the F344 and Sprague Dawley (SD) strains.

Sex and rat strain determine sensitivity to kappa opioid-induced antinociception.

Rationale: Recent studies indicate that sex and rodent strain are determinants of sensitivity to opioid-induced antinociception.

Objectives: The present study examined the influence of sex and rat strain on kappa opioid-induced antinociception using a series of kappa opioids that vary in their relative effectiveness.

Methods: In a warm-water (50, 52 and 55C) tail-withdrawal procedure, the antinociceptive effects of kappa opioids were determined in male and female rats of the F344, Lewis and Sprague-Dawley (SD) strains.