Electrolytic lesions and pharmacological inhibition of the dorsal raphe nucleus prevent stressor potentiation of morphine conditioned place preference in rats.

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Exposure to a single session of uncontrollable inescapable shock (IS), but not to identical controllable escapable shock, produces a potentiation of morphine's rewarding properties that is unusual in that the stressor can be given a number of days before the drug administration in an environment quite different from the drug context. Many other behavioral outcomes of stressors that depend on the uncontrollability of the stressor are mediated by alterations in serotonergic (5-HT) neurons within the dorsal raphe nucleus (DRN). The present experiments examined the role of the DRN and 5-HT in mediating the effect of IS on the rewarding properties of morphine as assessed by conditioned place preference (CPP). In experiment 1, subjects received small electrolytic lesions of the DRN and were tested for morphine (3.0 mg/kg, SC) CPP after IS or control treatment. In experiment 2, subjects received an intra-DRN microinjection of the 5-HT(1A) agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 1.0 microg/0.5 microl) either before IS or before morphine (3.0 mg/kg, SC) injections during CPP testing. IS potentiated morphine CPP in controls, but both DRN lesion and intra-DRN 8-OH-DPAT, either before IS or before morphine administration, completely blocked this effect. These data implicate alterations in DRN 5-HT neurons in the potentiation of morphine reward produced by uncontrollable stress.