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Single dose of morphine produced a prolonged effect on dopamine neuron activities.

Zhang D, Zhang H, Jin GZ, Zhang K, Zhen X - Mol Pain (2008)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: State Key Laboratory of Drug Research, Department of Neuropharmacology, Shanghai Institute of Material Medica, Chinese Academy of Sciences, Shanghai, PR China.

ABSTRACT

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.

Conclusion: 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.

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VTA DA neurons fail to response to subsequent challenge following a single morphine exposure. Rats received morphine (20 mg/kg, s.c.) or saline, and then challenged with morphine (5 mg/kg, i.v.) at 24 hours. A: firing rate. B: firing rate distribution in same neuron. C: representative segments of firing spike train before (upper panel) and after (low panel) the challenge. D: spectral charts before (upper panel) and after (low panel) the challenge.
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Figure 4: VTA DA neurons fail to response to subsequent challenge following a single morphine exposure. Rats received morphine (20 mg/kg, s.c.) or saline, and then challenged with morphine (5 mg/kg, i.v.) at 24 hours. A: firing rate. B: firing rate distribution in same neuron. C: representative segments of firing spike train before (upper panel) and after (low panel) the challenge. D: spectral charts before (upper panel) and after (low panel) the challenge.

Mentions: We next tested how VTA DA neuron responses to subsequent morphine challenge at different time points after initial exposure. In contrast to the activation of VTA DA neurons in response to morphine challenge in naïve rats (Figure. 1), morphine challenge (5 mg/kg, i.v.) at 24 hours after receiving the initial morphine exposure failed to alter the firing rate (-3.5 ± 3.3%, t-test, p = 0.322) or CV of ISIs (-13.0 ± 7.9%, t-test, p = 0.141) of the VTA DA neurons (Figure. 4 &5). Interestingly, the bursting (-36.4 ± 16.0%, t test, p < 0.05) was significantly decreased.


Single dose of morphine produced a prolonged effect on dopamine neuron activities.

Zhang D, Zhang H, Jin GZ, Zhang K, Zhen X - Mol Pain (2008)

VTA DA neurons fail to response to subsequent challenge following a single morphine exposure. Rats received morphine (20 mg/kg, s.c.) or saline, and then challenged with morphine (5 mg/kg, i.v.) at 24 hours. A: firing rate. B: firing rate distribution in same neuron. C: representative segments of firing spike train before (upper panel) and after (low panel) the challenge. D: spectral charts before (upper panel) and after (low panel) the challenge.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2603002&req=5

Figure 4: VTA DA neurons fail to response to subsequent challenge following a single morphine exposure. Rats received morphine (20 mg/kg, s.c.) or saline, and then challenged with morphine (5 mg/kg, i.v.) at 24 hours. A: firing rate. B: firing rate distribution in same neuron. C: representative segments of firing spike train before (upper panel) and after (low panel) the challenge. D: spectral charts before (upper panel) and after (low panel) the challenge.
Mentions: We next tested how VTA DA neuron responses to subsequent morphine challenge at different time points after initial exposure. In contrast to the activation of VTA DA neurons in response to morphine challenge in naïve rats (Figure. 1), morphine challenge (5 mg/kg, i.v.) at 24 hours after receiving the initial morphine exposure failed to alter the firing rate (-3.5 ± 3.3%, t-test, p = 0.322) or CV of ISIs (-13.0 ± 7.9%, t-test, p = 0.141) of the VTA DA neurons (Figure. 4 &5). Interestingly, the bursting (-36.4 ± 16.0%, t test, p < 0.05) was significantly decreased.

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: State Key Laboratory of Drug Research, Department of Neuropharmacology, Shanghai Institute of Material Medica, Chinese Academy of Sciences, Shanghai, PR China.

ABSTRACT

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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus