Opiate modulation of striatal dopamine and hippocampal norepinephrine release following morphine withdrawal.
When opiates are abruptly withdrawn after chronic treatment, increases in hippocampal noradrenergic function are observed which are accompanied by decreases in striatal dopamine release. The latter effects have to shown to persist for several weeks following the onset of opiate withdrawal. We examined the long-term effects of opiate withdrawal on 4-aminopyridine and potassium stimulated release of striatal dopamine and hippocampal norepinephrine. Tissue samples were obtained either from rats that had been exposed to opiate withdrawal following a seven day morphine infusion or sham treated control subjects. At 48 hours after the onset of withdrawal (cessation of morphine infusions), slices were loaded with [3H] neurotransmitter, washed extensively, and exposed to different drug treatments. 4-aminopyridine induced concentration related increases in striatal dopamine release, which was 36% calcium independent. Similar values for fractional release of striatal dopamine were obtained in morphine withdrawn and control subjects, for both potassium and 4-aminopyridine induced release. In addition, thresholds for 4-aminopyridine or potassium induced release of striatal dopamine did not differ between control and morphine withdrawn subjects. Treatment with 1.0 microM morphine sulfate potentiated potassium evoked release of norepinephrine to an equal extent in both morphine withdrawn and sham treated hippocampal tissue. Exposure to a threshold concentration of potassium (8.0 mM), stimulated increased release of hippocampal norepinephrine in a significantly greater fraction of tissue samples obtained from morphine withdrawn animals. Although these results do not support changes in striatal dopamine release following opiate withdrawal, opiate mechanisms appear to be important determinants of in vitro hippocampal norepinephrine release.
Grasing
K
K
Department of Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick 08903, USA.
Bills
D
D
Ghosh
S
S
Schlussman
S D
SD
Patel
A H
AH
Woodward
J J
JJ
D015761:4-Aminopyridine / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000009:adverse effects*; D000818:Animals; D002118:Calcium / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000009:adverse effects*; D009638:Norepinephrine / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013268:Stimulation, Chemical; D013375:Substance Withdrawal Syndrome
D000701:Analgesics, Opioid; D009020:Morphine; D015761:4-Aminopyridine; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine