Effect of age and long-term stress experience on adaptation to stress analgesia in mature rats: role of opioids.

The effects of aging and previous long-term stress on development of tolerance to stress-induced analgesia were evaluated in male Sprague-Dawley rats exposed to intermittent cold water swims (ICWS) in 2 degrees C water (eighteen 10-s exposure, three/min) on 15 consecutive days. Analgesia was measured by the tail-flick test prior to and 30 min after ICWS. In young rats (4 months), tolerance developed faster and asymptotic tolerance was acquired sooner and was more complete than in older rats (15-16 months). Previous long-term exposure (but not the age at which it occurred) accelerated the development and acquisition of asymptotic tolerance to reexposure. Naltrexone (10 mg/kg, ip) partially and completely reversed tolerance to ICWS analgesia in 4- and 9-10-month-old rats, respectively, results suggesting that the opioids are involved in ICWS-analgesia tolerance in both young and old mature rats. In young animals, a second mechanism, naltrexone-insensitive, may be responsible for at least some of the differences in ICWS tolerance found between young and old mature adult rats.