Low-Dose Δ9-THC Produces Antinociception in Female, But Not Male Rats.

Introduction: The analgesic effects of delta-9-tetrahydrocannabinol (THC), the primary psychoactive compound in cannabis, have been widely promoted. Unfortunately, animal research is limited by the use of high doses and pain-evoked tests. Motor and psychoactive effects of THC may suppress evoked responses in the absence of antinociceptive effects. Materials and Methods: This study overcomes these problems by assessing the antinociceptive effect of low doses of subcutaneous THC on depression of home cage wheel running caused by hindpaw inflammation. Female and male Long-Evans rats were individually housed in a cage with a running wheel. Results: Female rats ran significantly more than male rats. Administration of Complete Freund's Adjuvant into the right hindpaw produced inflammatory pain that significantly depressed wheel running in female and male rats. Administration of a low dose of THC (0.32, but not 0.56 or 1.0 mg/kg) restored wheel running in the hour after administration in female rats. Administration of these doses had no effect on pain-depressed wheel running in male rats. Conclusions: These data are consistent with previous studies showing greater antinociceptive effects of THC in female compared with male rats. These data extend previous findings by showing that low doses of THC can restore pain-depressed behaviors.

Comparative benefits of social housing and buprenorphine on wheel running depressed by morphine withdrawal in rats.

RATIONALE: Social support and opioid replacement therapy are commonly used to treat opioid withdrawal. OBJECTIVE: The present study tested the hypothesis that social housing and buprenorphine administration can restore wheel running depressed by morphine withdrawal in rats. RESULTS: Experiment 1 assessed disruptive side effects of buprenorphine and found that administration of low doses (3.2, 10, & 32 µg/kg, s.c.) had no impact on voluntary wheel running. Experiment 2 assessed the impact of social housing and acute buprenorphine administration (10 µg/kg) on morphine withdrawal. Two 75 mg morphine pellets were implanted for 3 days to induce dependence. Removal of the morphine pellets caused a decrease in body weight, increase in wet dog shakes, and depression of wheel running during the normally active dark phase of the circadian cycle. Social housing restored wheel running and reduced the number of wet dog shakes but did not affect body weight. Administration of buprenorphine restored wheel running depressed by morphine withdrawal for 2 days in individually housed rats and produced time-dependent changes in socially housed rats: Depression of wheel running in the 3 h following administration and restoration of running subsequently compared to saline-treated controls. CONCLUSIONS: The impact of buprenorphine and social housing to reduce the effect of morphine withdrawal in rats is consistent with the use of opioid substitution therapy and psychotherapy/social support to treat opioid withdrawal in humans. These data provide further validation for the clinical relevance for the use of wheel running to assess spontaneous opioid withdrawal.

Social housing promotes recovery of wheel running depressed by inflammatory pain and morphine withdrawal in male rats.

The increased use of opioids to treat pain has led to a dramatic increase in opioid abuse. Our previous data indicate that pain may facilitate the development of opioid abuse by increasing the magnitude and duration of opioid withdrawal. The present study tested the hypothesis that social housing would facilitate recovery of activity depressed by pain and opioid withdrawal. Male Sprague Dawley rats were housed either in pairs or alone and then moved to a cage with a running wheel for 6 h daily to assess pain- and opioid withdrawal-induced depression of wheel running. Rats were implanted with two morphine (75 mg each) or placebo pellets to induce opioid dependence and were simultaneously injected with Complete Freund's Adjuvant or saline into the right hind paw to induce persistent inflammatory pain. Hind paw inflammation depressed wheel running whether rats were implanted with a morphine or placebo pellet. Pair-housed rats showed greater recovery of wheel running than individually housed rats. Spontaneous morphine withdrawal precipitated by removal of the morphine pellets caused a reduction in wheel running that was greater in rats with hind paw inflammation compared to pain free rats. Social housing facilitated recovery from withdrawal in rats with hind paw inflammation, but slowed recovery in pain free rats. These data suggest that social housing facilitates recovery by reducing pain both before and during opioid withdrawal. Our findings are consistent with previous studies showing that social buffering reduces pain-evoked responses.