Anabolic–androgenic steroid effects on nociception and morphine antinociception in male rats

Abstract

The purpose of this study was to investigate the effects of acute and chronic administration of anabolic–androgenic steroids (AAS) on nociception and morphine antinociception in acute pain models, as well as on chronic inflammatory nociception. In Experiment 1, adult, gonadally intact male rats were injected s.c. for 28 days with either 5 mg/kg testosterone (T), dihydrotestosterone (DHT), stanozolol (STAN), or safflower oil vehicle (N = 12–25/group). On day 28, rats in each group were tested on acute thermal and mechanical nociceptive assays, before and after morphine treatment. In Experiment 2, rats in each group (N = 8–10/group) were injected with mineral oil or complete Freund's adjuvant (CFA) into one hindpaw after 28 days of AAS treatment, and then tested for thermal hyperalgesia, mechanical allodynia, inflammation and locomotor suppression intermittently for 28 days. Experiment 3 replicated nociceptive measurements in Experiments 1 and 2, but with a single AAS or vehicle injection occurring 3 h prior to testing (N = 10–12/group). While chronic AAS administration tended to decrease body weight gain and alter reproductive organ weights in the expected manner, it did not significantly alter acute nociception nor attenuate the development of various chronic pain indices after CFA administration. Morphine antinociceptive potency was significantly decreased by chronic DHT on the hotplate test only. Acute AAS administration also did not significantly alter acute or chronic nociception, or morphine antinociceptive potency. Comparisons between acute and chronic AAS administration suggest that steroid tolerance did not occur in rats treated with AAS chronically. Taken together, these data do not support the hypothesis that AAS exposure alters nociception or morphine antinociception in gonadally intact males.

Sex-specific effect of the anabolic steroid, 17α-methyltestosterone, on inhibitory avoidance learning in periadolescent rats

“…Consistently with this result, recent studies have shown that subcutaneous injections of testosterone, DHT, or stanozolol (5mg/kg; acute or chronic) did not alter pain nociception or induce chronic inflammatory pain in adult intact male rats (Tsutsui et al, 2011). However, we cannot rule out the possibility that 17 -meT elicited some kind of impulsivity effect, given that testosterone (5 mg/kg) displayed increased punished responses in the Vogel Conflict Test (Bing et al, 1998), although this measure is more associated with anxiolytic processes (Millan and Brocco, 2003) than to impulsivity.…”

Testosterone enhances risk tolerance without altering motor impulsivity in male rats

“…It is unlikely that this is due to proximate causes of increased hunger or insensitivity to pain. Chronic treatment with testosterone and other AAS at high doses in male rats does not increase food consumption (Bisschop et al, 1997; Lindblom et al, 2003) or reduce responsiveness to pain, including acute thermal and mechanical nociceptive stimuli applied to the paws as in the present study (Celerier et al 2003; Tsutsui et al, 2011). Instead, it might appear that testosterone reduces aspects of cognitive flexibility, to favor a “win-at-all- costs” approach to maximizing gains.…”

TREK1 channel activation as a new analgesic strategy devoid of opioid adverse effects

“…The intraplantar injection volume in rats was 200 μl. Positive controls were used at the following doses: 5 mg·kg −1 morphine in rats for analgesia (Tsutsui, Wood, & Craft, 2011), 3 mg·kg −1 morphine in mice for analgesia and constipation (Devilliers et al, 2013), 50 mg·kg −1 morphine in mice for respiratory depression (Devilliers et al, 2013), 15 mg·kg −1 morphine in mice for place preference conditioning (Francès, Smirnova, Leriche, & Sokoloff, 2004), 10 mg·kg −1 duloxetine for screening tests of antidepressant drugs (Zomkowski, Engel, Cunha, Gabilan, & Rodrigues, 2012) and 100 mg·kg −1 gabapentin in rats for neuropathic pain relief (Urban et al, 2005).…”