Tolerance to the antinociceptive effect of morphine in the spinal rat

Tolerance and withdrawal were studied in spinal and intact rats receiving morphine hydrochloride (10–20 mg/kg, i.p.) every 12 hr for 10 days. All rats developed tolerance to morphine-induced antinociception measured by the tail-flick method. Tolerance was not reversed by d,l-5-hydroxytryptophan (200 mg/kg, i.p.). Naloxone (1–2 mg/kg) induced signs of withdrawal both in spinal and intact rats. Thus, functional changes in the aminergic systems and in brain and brainstem structures appear not to be necessary for tolerance to morphine-induced antinociception and for dependence on morphine. The experiment does not support the hypothesis that conditioning to environmental stimuli and changes in cognitive functions play a major role in tolerance development in the rat.