Single dose of morphine produced a prolonged effect on dopamine neuron activities.
BACKGROUND
Clinical observation and experimental studies have indicated that a single exposure to morphine could induce tolerance and dependence. It has become a concern in clinical antinociceptive practice. However, the underling mechanism remains unknown. This study was designed to explore the changes of dopamine (DA) neuron activities in the ventral tegmental area (VTA) by employing a spectral analysis followed single morphine treatment.


RESULTS
Acute morphine treatment significantly increased not only the firing rate and firing population but also the power of slow oscillation of DA neurons in naïve rats. These changes lasted at least for 3 days following the morphine treatment. During this period of time, responses of the DA neurons to subsequent morphine challenge were diminished. We further demonstrated a transient desensitization of opiate receptors as monitored by GTPgammaS binding to G-proteins. The present study provided first direct evidence for the temporal changes in the VTA DA neuron activities and opiate receptors desensitization.


CONCLUSIONS
Prolonged VTA DA neuron activation and opiate receptors desensitization followed single morphine exposure may underlie the development of dependence and tolerance that may associate with the acute analgesic tolerance and acute addiction of morphine.
Zhang
Die
D
State Key Laboratory of Drug Research, Department of Neuropharmacology, Shanghai Institute of Material Medica, Chinese Academy of Sciences, Shanghai, PR China.
Zhang
Hai
H
Jin
Guo-Zhang
GZ
Zhang
Kehong
K
Zhen
Xuechu
X
D000818:Animals; D004298:Dopamine; D004361:Drug Tolerance; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects; D019966:Substance-Related Disorders / Q000209:etiology; D013997:Time Factors
D011957:Receptors, Opioid; D009020:Morphine; D004298:Dopamine