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 morphine tolerance and dependence was investigated in mice. DSP-4 pretreatment, either 50 or 100 mg/kg i.p., had no effect on the development of tolerance to the analgesic effect of morphine evaluated by the tail-flick test. On the contrary, the higher dose of DSP-4 prevented repetitive vertical jumping, a major naloxone-precipitated withdrawal symptom in mice. These results demonstrate that coerulean neuronal projections are not necessary for the development of tolerance but are clearly involved in the expression of withdrawal-induced jumping in mice.