Psychopharmacology
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Gonadal steroid hormones altered opioid antinociception under some conditions in rodents, and we reported previously that chronic estradiol enhanced kappa but not mu opioid antinociception in ovariectomized rhesus monkeys. Sex differences have also been observed in the antinociceptive effects of opioid agonists. These findings suggest that gonadal hormones may modulate opioid antinociception. ⋯ These findings further suggest that chronic treatment with physiological levels of gonadal hormones may modulate the antinociceptive effects of U50,488 in ovariectomized rhesus monkeys.
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Recreational drug use is increasingly widespread amongst young people, but there are concerns that psychoactive drugs may be associated with psychiatric symptoms or psychobiological problems. ⋯ The recreational use of ecstasy/MDMA is associated with a range of psychiatric symptoms and psychobiological problems. However, these problems are not specific to ecstasy users but are also evident in other recreational polydrug users.
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Comparative Study
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.
Recent studies indicate that mu opioids are generally more potent and effective as antinociceptive agents in male than female rodents. ⋯ That comparable levels of morphine tolerance were obtained in males and females when the functional chronic morphine dose was taken into consideration suggests that the mechanism underlying tolerance is not sex-dependent. Sex differences in the effectiveness of buprenorphine and dezocine when administered acutely and during chronic morphine administration further suggest that these opioids have lower efficacy at the mu opioid receptor in females.
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Psychological dependence to the opioid analgesic morphine is attributable to the rewarding properties of the drug, and its evolution can be divided into two distinct phases: development and maintenance. Both phases can be studied using conditioned place preference (CPP). ⋯ Neither gabapentin nor pregabalin induced CPP, but both compounds blocked the development of CPP to morphine and also blocked morphine's effects on dopamine release. Furthermore, pregabalin blocked the maintenance of morphine-induced CPP. It is concluded that gabapentin-like compounds, which have no intrinsic rewarding properties, may have some therapeutic use in the treatment of opioid dependence.
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Randomized Controlled Trial Comparative Study Clinical Trial
Enadoline, a selective kappa opioid agonist: comparison with butorphanol and hydromorphone in humans.
The availability of the highly selective and specific kappa opioid agonist enadoline provides an opportunity to explore the function of kappa receptors in humans and their potential utility as a target for substance abuse pharmacotherapy development. ⋯ These results are discussed with respect to the potential use and safety of kappa agonists for clinical indications.