Lesions to terminals of noradrenergic locus coeruleus neurones do not inhibit opiate withdrawal behaviour in rats.

The involvement of neurones of the locus coeruleus (LC) in expression of opiate withdrawal behaviour was tested in morphine-dependent rats using N-2-chloroethyl-N-ethyl-2-bromobenzylamine (DSP4), a neurotoxin selective for noradrenergic terminals arising from LC. Lesions were validated by determination of cortical noradrenaline concentrations using gas chromatography-mass spectrometry, inhibition of the post-decapitation hindpaw reflex and dopamine-beta-hydroxylase immunohistochemistry. Lesions did not inhibit the expression of any naloxone-precipitated withdrawal signs. These results suggest no involvement of noradrenergic LC neurones in expression of the overt signs of opiate withdrawal, and raise the possibility that previous microinjection and electrolytic lesion studies were confounded by effects on nearby brain regions.