Morphine tolerance and dependence in the locus coeruleus: single cell studies in brain slices

Extracellular single unit recordings in vitro from the locus coeruleus in rat brainstem slices revealed the presence of spontaneously active neurons. These cells fired between 0.1 and 3.0 spikes/s and were inhibited by nM concentrations of morphine and clonidine. Locus coeruleus neurons in slices from animals treated chronically, but not subacutely, with morphine exhibited a significant decrease in sensitivity to morphine. This tolerance appeared to be specific for opiates since no decrease in sensitivity was seen for the alpha 2-adrenoceptor agonist clonidine. However, in contrast to what has been reported in vivo, no signs of dependence (withdrawal activation) were evident in slices from morphine tolerant animals.