The kappa-opioid receptor is upregulated in the spinal cord and locus ceruleus but downregulated in the dorsal root ganglia of morphine tolerant rats

Li, Xuan-ying; Sun, Li; He, Jie; Chen, Zhao-li; Zhou, Fang; Liu, Xiaoyan; Liu, Ruo-shan

doi:10.1016/j.brainres.2010.02.070

Cited by 15 publications

(8 citation statements)

References 49 publications

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“…However, there is evidence to suggest remarkable increases in specific variants of mu receptors mRNA levels in the specific regions of the brain such as the hypothalamus and hippocampus following long-term use of morphine (Xu et al, 2015). Also, an up-regulation of kappa opioid receptors in the locus coeruleus and spinal cord but a down-regulation in the DRG was observed in morphine-tolerant rats (Li et al, 2010). In the hippocampus, mu and delta opioid receptors predominantly are located on overlapping presynaptic populations of GABAergic neurons modulating principal glutamatergic cells activity (Erbs et al, 2016).…”

Section: Opioid Receptors Expression Profiles After Rmementioning

confidence: 99%

A distinct impact of repeated morphine exposure on synaptic plasticity at Schaffer collateral‐CA1, temporoammonic‐CA1, and perforant pathway‐dentate gyrus synapses along the longitudinal axis of the hippocampus

et al. 2022

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We aimed to study how morphine affects synaptic transmission in the dentate gyrus and CA1 regions along the hippocampal long axis. For this, recording and measuring of field excitatory postsynaptic potentials (fEPSPs) were utilized to test the effects of repeated morphine exposure on paired-pulse evoked responses and long-term potentiation (LTP) at Schaffer collateral-CA1 (Sch-CA1), temporoammonic-CA1 (TA-CA1) and perforant pathway-dentate gyrus (PP-DG) synapses in transverse slices from the dorsal (DH), intermediate (IH), and ventral (VH) hippocampus in adult male rats. After repeated morphine exposure, the expression of opioid receptors and the α1 and α5 GABA A subunits were also examined. We found that repeated morphine exposure blunt the difference between the DH and the VH in their basal levels of synaptic transmission at Sch-CA1 synapses that were seen in the control groups. Significant paired-pulse facilitation of excitatory synaptic transmission was observed at Sch-CA1 synapses in slices taken from all three hippocampal segments as well as at PP-DG synapses in slices taken from the VH segment in the morphine-treated groups as compared to the control groups. Interestingly, significant paired-pulse inhibition of excitatory synaptic transmission was observed at TA-CA1 synapses in the DH slices from the morphine-treated group as compared to the control group. While primedburst stimulation (a protocol reflecting normal neuronal firing) induced a robust LTP in hippocampal subfields in all control groups, resulting in a decaying LTP at TA-CA1 synapses in the VH slices and at PP-DG synapses in both the IH and VH slices taken from the morphine-treated rats. In the DH of morphine-treated rats, we found increased levels of the mRNAs encoding the α1 and α5 GABA A subunits as compared to the control group. Taken together, these findings suggest the potential mechanisms through which repeated morphine exposure causes differential changes in circuit excitability and synaptic plasticity in the dentate gyrus and CA1 regions along the hippocampal long axis.

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Section: Opioid Receptors Expression Profiles After Rmementioning

confidence: 99%

A distinct impact of repeated morphine exposure on synaptic plasticity at Schaffer collateral‐CA1, temporoammonic‐CA1, and perforant pathway‐dentate gyrus synapses along the longitudinal axis of the hippocampus

et al. 2022

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“…Chronic opioid exposure could upregulate KOR (X.‐Y. Li et al, 2010; Suzuki, Chuang, Chuang, Doi, & Chuang, 2001) and downregulate MOR (Tempel, Habas, Paredes, & Barr, 1988; Turchan et al, 1999; Zadina, Chang, Ge, & Kastin, 1993), which may have contributed to dorsal striatal NAL‐DA release in OUD.…”

Section: Discussionmentioning

confidence: 99%

Brain opioid segments and striatal patterns of dopamine release induced by naloxone and morphine

Shokri‐Kojori

Naganawa

Ramchandani

et al. 2021

Human Brain Mapping

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Opioid receptors are expressed throughout the brain and play a major role in regulating striatal dopamine (DA) release. Clinical studies have shown that naloxone (NAL, a nonspecific opioid antagonist) in individuals with opioid use disorder and morphine (MRP, a nonspecific opioid agonist) in healthy controls, resulted in DA release in the dorsal and ventral striatum, respectively. It is not known whether the underlying patterns of striatal DA release are associated with the striatal distribution of opioid receptors. We leveraged previously published PET datasets (collected in independent cohorts) to study the brain‐wide distribution of opioid receptors and to compare striatal opioid receptor availability with striatal DA release patterns. We identified three major gray matter segments based on availability maps of DA and opioid receptors: striatum, and primary and secondary opioid segments with high and intermediate opioid receptor availability, respectively. Patterns of DA release induced by NAL and MRP were inversely associated and correlated with kappa (NAL: r(68) = −0.81, MRP: r(68) = 0.54), and mu (NAL: r(68) = −0.62, MRP: r(68) = 0.46) opioid receptor availability. Kappa opioid receptor availability accounted for a unique part of variance in NAL‐ and MRP‐DA release patterns (ΔR2 >0.14, p <.0001). In sum, distributions of opioid receptors distinguished major cortical and subcortical regions. Patterns of NAL‐ and MRP‐induced DA release had inverse associations with striatal opioid receptor availability. Our approach provides a pattern‐based characterization of drug‐induced DA targets and is relevant for modeling the role of opioid receptors in modulating striatal DA release.

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“…The occurrence of bone cancer pain involves multiple pathophysiological mechanisms, and satisfactory analgesic results are often difficult to achieve with a particular drug [ 24 , 25 ]. In recent years, multimodal analgesia has been widely accepted and used in the treatment of bone cancer pain [ 13 ]. Although dezocine is often clinically combined with morphine to manage pain, their clinical effect is still controversial [ 5 , 26 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of dezocine on morphine tolerance and opioid receptor expression in a rat model of bone cancer pain

Dong

Zhu

et al. 2021

BMC Cancer

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Background Clinically, the coadministration of opioids to enhance antinociception and decrease tolerance has attracted increasing research attention. We investigated the effects of dezocine, a mu- and kappa-opioid receptor agonist/antagonist, on morphine tolerance and explored the involvement of opioid receptor expression in a rat model of bone cancer pain. Methods Thermal nociceptive thresholds were measured after the subcutaneous injection of morphine (10 mg/kg) alone or combined with dezocine (10 or 1 mg/kg) for 7 consecutive days. Real-time PCR and western blot analysis were used to examine opioid receptor expression in the periaqueductal gray (PAG) and spinal cord. Results The analgesic effect was significantly decreased after 4 days of morphine administration. We observed that low-dose dezocine significantly attenuated morphine tolerance without reducing the analgesic effect of morphine. Low-dose dezocine coadministration significantly reversed the downregulated expression of mu (MOR) and delta (DOR) opioid receptors in the PAG and the upregulated expression of kappa (KOR) and DOR in the spinal cord induced by morphine. Moreover, low-dose dezocine coadministered with morphine significantly inhibited KOR expression in both the PAG and spinal cord. Conclusions The combination of low-dose dezocine with morphine may prevent or delay the development of morphine tolerance in a rat model of bone cancer pain. The regulation of opioid receptor expression in the PAG and spinal cord may be part of the mechanism.

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The kappa-opioid receptor is upregulated in the spinal cord and locus ceruleus but downregulated in the dorsal root ganglia of morphine tolerant rats

Cited by 15 publications

References 49 publications

A distinct impact of repeated morphine exposure on synaptic plasticity at Schaffer collateral‐CA1, temporoammonic‐CA1, and perforant pathway‐dentate gyrus synapses along the longitudinal axis of the hippocampus

A distinct impact of repeated morphine exposure on synaptic plasticity at Schaffer collateral‐CA1, temporoammonic‐CA1, and perforant pathway‐dentate gyrus synapses along the longitudinal axis of the hippocampus

Brain opioid segments and striatal patterns of dopamine release induced by naloxone and morphine

Effects of dezocine on morphine tolerance and opioid receptor expression in a rat model of bone cancer pain

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