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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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Single morphine exposure alters firing pattern of VTA DA neurons. Rats received morphine (20 mg/kg, s.c.) or saline. A: spectral charts at 24, 72, 120 hours after the treatment. B: group summary. *P < 0.05, compared to saline control. Mor: morphine.
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Figure 3: Single morphine exposure alters firing pattern of VTA DA neurons. Rats received morphine (20 mg/kg, s.c.) or saline. A: spectral charts at 24, 72, 120 hours after the treatment. B: group summary. *P < 0.05, compared to saline control. Mor: morphine.

Mentions: As depicted in Figure. 2 &3, at 24 hours after morphine exposure (20 mg/kg, s.c.), firing rate of the VTA DA neurons was significantly higher than that in the control rats receiving saline (3.99 ± 0.14 spikes/sec, t-test, p < 0.05, compared to saline control). Bursting (20.96 ± 2.12%, p < 0.001), CV of ISIs (69.66 ± 2.40%, p < 0.001) and the number of firing VTA DA cells/track (1.74 ± 0.10 cells/track, p < 0.05). SO power (1.39 ± 0.17, p < 0.05, compared to control) were also significantly higher than the corresponding measures in the control rats receiving saline.


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)

Single morphine exposure alters firing pattern of VTA DA neurons. Rats received morphine (20 mg/kg, s.c.) or saline. A: spectral charts at 24, 72, 120 hours after the treatment. B: group summary. *P < 0.05, compared to saline control. Mor: morphine.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Single morphine exposure alters firing pattern of VTA DA neurons. Rats received morphine (20 mg/kg, s.c.) or saline. A: spectral charts at 24, 72, 120 hours after the treatment. B: group summary. *P < 0.05, compared to saline control. Mor: morphine.
Mentions: As depicted in Figure. 2 &3, at 24 hours after morphine exposure (20 mg/kg, s.c.), firing rate of the VTA DA neurons was significantly higher than that in the control rats receiving saline (3.99 ± 0.14 spikes/sec, t-test, p < 0.05, compared to saline control). Bursting (20.96 ± 2.12%, p < 0.001), CV of ISIs (69.66 ± 2.40%, p < 0.001) and the number of firing VTA DA cells/track (1.74 ± 0.10 cells/track, p < 0.05). SO power (1.39 ± 0.17, p < 0.05, compared to control) were also significantly higher than the corresponding measures in the control rats receiving saline.

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