INVOLVEMENT OF LOCUS-COERULEUS PROJECTIONS IN OPIATE WITHDRAWAL BUT NOT IN OPIATE TOLERANCE IN MICE

The ability of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), a potent and selective noradrenergic neurotoxic compound, to modify mor phine tolerance and dependence was investigated in mice. DSP-4 pretrea tment, either 50 or 100 mg/kg i.p., had no effect on the development o f tolerance to the analgesic effect of morphine evaluated by the tail- flick test. On the contrary, the higher dose of DSP-4 prevented repeti tive vertical jumping, a major naloxone-precipitated withdrawal sympto m in mice. These results demonstrate that coerulean neuronal projectio ns are not necessary for the development of tolerance but are clearly involved in the expression of withdrawal-induced jumping in mice.