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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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Related in: MedlinePlus

Slow oscillation (SO) of VTA DA neuron is time-dependently changed in response to morphine challenge after a single morphine exposure. Rats received morphine (20 mg/kg, s.c.) or saline, and then challenged with morphine (5 mg/kg, i.v.) 24, 72 or 120 hours later. A: representative spectral chart. B: group summary. *P < 0.05, Paired t test, compared to respective control.
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Figure 6: Slow oscillation (SO) of VTA DA neuron is time-dependently changed in response to morphine challenge after a single morphine exposure. Rats received morphine (20 mg/kg, s.c.) or saline, and then challenged with morphine (5 mg/kg, i.v.) 24, 72 or 120 hours later. A: representative spectral chart. B: group summary. *P < 0.05, Paired t test, compared to respective control.

Mentions: The failure of the VTA DA neurons in response to morphine challenge lasted at least 72 hours as depicted in firing rate (+0.9 ± 5.1%, t -test, p = 0.867), bursting (+6.0 ± 36.4%, t test, p = 0.875), CV of ISIs (-11.6 ± 8.5%, t -test, p = 0.209) and SO power. This indicated that VTA DA neurons developed a tolerance followed the single dose of morphine pretreatment. However, the response of DA neurons to morphine challenge was restored at 120 hours (Figure. 5): the firing rate was increased by 34.1 ± 10.6% (t-test, p < 0.05); The SO power, as shown in Fig. 6, was significantly decreased (-41.8 ± 13.2%, t-test, p < 0.05) at 24 h after initial morphine exposure, and was started to recover at 72 h (+24.6 ± 23.7%, t- test, p = 0.331), restored at 120 h(118.5 ± 62.0%, t-test, p < 0.05). Taken together, the present data demonstrated that single morphine administration results in prolonged unresponsiveness of VTA DA neurons to subsequent morphine challenge which lasted at least three days.


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)

Slow oscillation (SO) of VTA DA neuron is time-dependently changed in response to morphine challenge after a single morphine exposure. Rats received morphine (20 mg/kg, s.c.) or saline, and then challenged with morphine (5 mg/kg, i.v.) 24, 72 or 120 hours later. A: representative spectral chart. B: group summary. *P < 0.05, Paired t test, compared to respective control.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: Slow oscillation (SO) of VTA DA neuron is time-dependently changed in response to morphine challenge after a single morphine exposure. Rats received morphine (20 mg/kg, s.c.) or saline, and then challenged with morphine (5 mg/kg, i.v.) 24, 72 or 120 hours later. A: representative spectral chart. B: group summary. *P < 0.05, Paired t test, compared to respective control.
Mentions: The failure of the VTA DA neurons in response to morphine challenge lasted at least 72 hours as depicted in firing rate (+0.9 ± 5.1%, t -test, p = 0.867), bursting (+6.0 ± 36.4%, t test, p = 0.875), CV of ISIs (-11.6 ± 8.5%, t -test, p = 0.209) and SO power. This indicated that VTA DA neurons developed a tolerance followed the single dose of morphine pretreatment. However, the response of DA neurons to morphine challenge was restored at 120 hours (Figure. 5): the firing rate was increased by 34.1 ± 10.6% (t-test, p < 0.05); The SO power, as shown in Fig. 6, was significantly decreased (-41.8 ± 13.2%, t-test, p < 0.05) at 24 h after initial morphine exposure, and was started to recover at 72 h (+24.6 ± 23.7%, t- test, p = 0.331), restored at 120 h(118.5 ± 62.0%, t-test, p < 0.05). Taken together, the present data demonstrated that single morphine administration results in prolonged unresponsiveness of VTA DA neurons to subsequent morphine challenge which lasted at least three days.

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