hydrocodone and Alcoholism

A monthly extended-release formulation of the opioid antagonist naltrexone (XR-NTX) is approved for treatment of alcohol dependence. There is little research regarding overriding chronic (>21 days) competitive opioid receptor blockade with opioids for acute pain. Using the hot plate test after XR-NTX or placebo microsphere administration, rats were treated with an opioid analgesic to determine the dose required to produce the maximum response latency (MRL; 60 s). Rats were later treated with the same opioid to determine any potential effects on respiration rate or locomotor activity. In naïve rats, 15 mg/kg morphine, 0.1 mg/kg fentanyl and 8 mg/kg hydrocodone produced MRL. In XR-NTX treated rats, morphine produced 36% and 46% MRL at 90 mg/kg on days 4 and 19 and 96% MRL at 45 mg/kg on day 39. Fentanyl produced 100% MRL at 2.0 mg/kg on days 4 and 19 and at 0.5 mg/kg on day 39. Hydrocodone (80 mg/kg) produced 69%, 80% and 100% MRL on days 4, 19 and 39. Compared to placebo, these doses did not further depress respiration or alter locomotor activity. Thus, opioid receptor blockade with XR-NTX can be overcome in rats with higher doses of opioids without further affecting respiration or locomotor activity.

Topics: Alcoholism; Analgesics, Opioid; Animals; Delayed-Action Preparations; Drug Interactions; Fentanyl; Humans; Hydrocodone; Male; Morphine; Motor Activity; Naltrexone; Narcotic Antagonists; Pain; Pain Measurement; Plethysmography, Whole Body; Rats; Rats, Sprague-Dawley; Respiration