The brain stem but not forebrain independently supports morphine tolerance and withdrawal effects in cats.

Abstract We employed polygraphic recordings and behavioral measures to study the effects of chronic morphine use upon the isolated forebrain and the decerebrate animal in cats with a midbrain transection. Cats received morphine for 12 days, and 24 h recording sessions were conducted on days 1 and 11. For the decerebrate cat, the percent time of rapid eye movement (REM) sleep was reduced during the 24 h period on both days 1 and 11. However, the values on day 11 were consistently higher than the values on day 1. Other tolerance indicators were decreases in the number of early behavioral signs and in the onset delay for REM sleep, together with an increase in onset time for motor activation. After naloxone (day 12) all cats displayed “wet shakes,” tachypnea and eye squinting, as well as either pyloerection, elevated tail, salivation, licking, micturition, and yawning. In the isolated forebrain , the percent time for waking increased through the first 18 h post-morphine on both days 1 and 11. Conversely, the duration of non-REM (NREM) sleep and of drowsiness decreased. But importantly, the duration of sleep–waking states did not vary between days 11 and 1, indicating absence of tolerance. Additionally, after naloxone, the isolated forebrain entered NREM sleep, contrasting with opposite findings in intact cats. Therefore, while we could not demonstrate chronic use effects in the isolated forebrain, the decerebrate cat still displayed typical tolerance/withdrawal manifestations. This suggests that the effects of chronic opiate use are deeply seated in the brain stem, which might help understanding the ingrained nature of physical dependence.