OPIATE MODULATION OF STRIATAL DOPAMINE AND HIPPOCAMPAL NOREPINEPHRINERELEASE FOLLOWING MORPHINE-WITHDRAWAL

When opiates are abruptly withdrawn after chronic treatment, increases in hippocampal noradrenergic function are observed which are accompan ied by decreases in striatal dopamine release. The latter effects have to shown to persist for several weeks following the onset of opiate w ithdrawal. We examined the long-term effects of opiate withdrawal on 4 -aminopyridine and potassium stimulated release of striatal dopamine a nd hippocampal norepinephrine. Tissue samples were obtained either fro m rats that had been exposed to opiate withdrawal following a seven da y morphine infusion or sham treated control subjects. At 48 hours afte r the onset of withdrawal (cessation of morphine infusions), slices we re loaded with [H-3] neurotransmitter, washed extensively, and exposed to different drug treatments. 4-aminopyridine induced concentration r elated increases in striatal dopamine release, which was 36% calcium i ndependent. Similar values for fractional release of striatal dopamine were obtained in morphine withdrawn and control subjects, for both po tassium and 4-aminopyridine induced release. In addition, thresholds f or 4-aminopyridine or potassium induced release of striatal dopamine d id not differ between control and morphine withdrawn subjects. Treatme nt with 1.0 mu M morphine sulfate potentiated potassium evoked release of norepinephrine to an equal extent in both morphine withdrawn and s ham treated hippocampal tissue. Exposure to a threshold concentration of potassium (8.0 mM), stimulated increased release of hippocampal nor epinephrine in a significantly greater fraction of tissue samples obta ined from morphine withdrawn animals. Although these results do not su pport changes in striatal dopamine release following opiate withdrawal , opiate mechanisms appear to be important determinants of in vitro hi ppocampal norepinephrine release.