Role of Cerebral Dopamine and Noradrenaline in the Morphine-induced Locomotor Sensitisation in Mice

Abstract

The effects of morphine on locomotor activity and cerebral dopamine (DA) and noradrenaline (NA) metabolism were studied in mice treated repeatedly with morphine for 5 days followed by 1, 3, or 5 days of withdrawal. Acute morphine treatment did not increase the locomotor activity of mice withdrawn for 1 day, after withdrawal for 3 days the increase was similar to that in controls, and after 5 days the increase was clearly larger than in controls. In mice withdrawn for 3 or 5 days, but not in control mice, acute morphine significantly elevated striatal 3,4-dihydroxyphenylacetic acid and homovanillic acid concentrations. Acute morphine challenge decreased striatal 3-methoxytyramine in control mice, but did not alter it in mice withdrawn for 3 or 5 days. In mice withdrawn for 3 days acute morphine increased the free 3-methoxy-4-hydroxyphenylethylene glycol in all brain areas studied clearly less than in controls, whereas in mice withdrawn for 5 days the tolerance was found only in the hypothalamus. Our results show that the morphine-induced locomotor hyperactivity is enhanced in mice after sufficiently long withdrawal, when mice are sensitised to the acute morphine-induced increase of DA turnover but the tolerance to morphine’s effects on cerebral NA is disappearing, suggesting that in mice the cerebral NAergic systems, in addition to the DAergic ones, are major determinants of the behavioural response to morphine.