Repeated morphine exposure decreased the nucleus accumbens excitability during short-term withdrawal.
It is well known that the nucleus accumbens plays an important role in drug reinforcing effect and relapse. However, the cellular neuroadaptations that take place in accumbens neurons after repeated drug exposure are still not well understood, especially for opioids. Here, we examined how nucleus accumbens neuronal excitability becomes affected in rats exposed to morphine using whole-cell patch-clamp recordings. Medium spiny neurons recorded from brain slices of repeated morphine treated rats exhibited a significant decrease in the intrinsic excitability after 3-4 days withdrawal, compared to that of neurons from saline treated animals, which was indicated by the increase of current to evoke the first spike and the decrease of spike number induced by depolarizing current steps in the morphine group. Moreover, the excitability decrease was accompanied by related membrane property changes, such as resting membrane potential hyperpolarization, input resistance, and membrane time constant decrease, inward rectification increase, and action potential duration decrease. Taken together, repeated morphine exposure and short-term withdrawal may reduce nucleus accumbens activity and output by modulating intrinsic membrane properties of its output neurons, which could be an important neuroadaptation process that mediates morphine addictive effect.
Heng
Li-Jun
LJ
Institute of Neuroscience, Fourth Military Medical University, Xi'an, Shaanxi 710032, People's Republic of China.
Yang
Jing
J
Liu
Yi-Hui
YH
Wang
Wen-Ting
WT
Hu
San-Jue
SJ
Gao
Guo-Dong
GD
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D009021:Morphine Dependence / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D013997:Time Factors
D009020:Morphine