Extracellular Signal-Regulated Kinase in Nucleus Accumbens Mediates Propofol Self-Administration in Rats

Wang, Benfu; Yang, Xiaowei; Sun, Anna; Xu, Lei; Wang, Sicong; Lin, Wenhua; Lai, Ming-Kuen; Zhu, Huaqiang; Zhou, Wenhua; Lian, Qingquan

doi:10.1007/s12264-016-0066-1

Cited by 29 publications

(28 citation statements)

References 37 publications

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“…19,20 Serving as key nociceptive signals in glial cells, ERK is activated and mediated neuron sensitization under pain conditions. Several experiments have shown that ERK are prone to be phosphorylated after the activation of some chemokine receptors.…”

Section: Introductionmentioning

confidence: 99%

Up-regulation of CXCR4 expression contributes to persistent abdominal pain in rats with chronic pancreatitis

Miao

Wang

et al. 2017

Mol Pain

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BackgroundPain in patients with chronic pancreatitis is critical hallmark that accompanied inflammation, fibrosis, and destruction of glandular pancreas. Many researchers have demonstrated that stromal cell-derived factor 1 (also named as CXCL12) and its cognate receptor C-X-C chemokine receptor type 4 (CXCR4) involved in mediating neuropathic and bone cancer pain. However, their roles in chronic pancreatic pain remain largely unclear.MethodsChronic pancreatitis was induced by intraductal injection of trinitrobenzene sulfonic acid to the pancreas. Von Frey filament tests were conducted to evaluate pancreas hypersensitivity of rat. Expression of CXCL12, CXCR4, NaV1.8, and pERK in rat dorsal root ganglion was detected by Western blot analyses. Dorsal root ganglion neuronal excitability was assessed by electrophysiological recordings.ResultsWe showed that both CXCL12 and CXCR4 were dramatically up-regulated in the dorsal root ganglion in trinitrobenzene sulfonic acid-induced chronic pancreatitis pain model. Intrathecal application with AMD3100, a potent and selective CXCR4 inhibitor, reversed the hyperexcitability of dorsal root ganglion neurons innervating the pancreas of rats following trinitrobenzene sulfonic acid injection. Furthermore, trinitrobenzene sulfonic acid-induced extracellular signal-regulated kinase activation and Nav1.8 up-regulation in dorsal root ganglias were reversed by intrathecal application with AMD3100 as well as by blockade of extracellular signal-regulated kinase activation by intrathecal U0126. More importantly, the trinitrobenzene sulfonic acid-induced persistent pain was significantly suppressed by CXCR4 and extracellular signal-regulated kinase inhibitors.ConclusionsThe present results suggest that the activation of CXCL12–CXCR4 signaling might contribute to pancreatic pain and that extracellular signal-regulated kinase-dependent Nav1.8 up-regulation might lead to hyperexcitability of the primary nociceptor neurons in rats with chronic pancreatitis.

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Section: Introductionmentioning

confidence: 99%

Up-regulation of CXCR4 expression contributes to persistent abdominal pain in rats with chronic pancreatitis

Miao

Wang

et al. 2017

Mol Pain

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“…We have previously demonstrated a role for GABA receptors in the ventral tegmental area (VTA) as regulators of propofol self-administration behavior [6]. We further found that the D1R antagonist SCH23390 was able to mediate a simultaneous dose-dependent reduction in propofol selfadministration while also decreasing D1R-associated p-ERK/ERK levels in the nucleus accumbens (NAc) [7,8]. These previous results clearly indicate that propofol is susceptible to abuse, although the mechanistic basis for this susceptibility remains uncertain.…”

Section: Introductionmentioning

confidence: 95%

The Role of NMDA receptors in rat propofol self-administration

Chen

Huang

Dong

et al. 2020

Preprint

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Background: Propofol is among the most frequently used anesthetic agents, and it has the potential for abuse. The N-methyl-D-aspartate (NMDA) receptors are key mediators neural plasticity, neuronal development, addiction, and neurodegeneration. In the present study, we explored the role of these receptors in the context of rat propofol self-administration. Methods: Sprague-Dawley Rats were trained to self-administer propofol (1.7 mg/kg/infusion) using a fixed-ratio (FR) schedule over the course of 14 sessions (3 h/day). After training, rats were intraperitoneally administered the non-competitive NDMA receptor antagonist MK-801, followed 10 minutes later by a propofol self-administration session. Results: After training, rats successfully underwent acquisition of propofol self-administration, as evidenced by a significant and stable rise in the number of active nose-pokes resulting in propofol administration relative to the number of control inactive nose-pokes (P<0.01). As compared to control rats, rats that had been injected with 0.2 mg/kg MK-801 exhibited a significantly greater number of propofol infusions (F (3, 28) = 4.372, P<0.01), whereas infusions were comparable in the groups administered 0.1 mg/kg and 0.4 mg/kg of this compound. In addition, MK-801 failed to alter the numbers of active (F (3, 28) = 1.353, P>0.05) or inactive (F (3, 28) = 0.047, P>0.05) responses in these study groups. Animals administered 0.4 mg/kg MK-801 exhibited significantly fewer infusions than animals administered 0.2 mg/kg MK-801 (P=0.006, P<0.01). In contrast, however, animals in the 0.4 mg/kg MK-801 group displayed a significant reduction in the number of active nose-poke responses (F(3, 20)=20.8673, P<0.01) and the number of sucrose pellets (F(3, 20)=23.77, P<0.01), while their locomotor activity was increased (F(3, 20)=22.812, P<0.01). Conclusion: These findings indicate that NMDA receptors may play a role in regulating rat self-administration of propofol.

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“…Since then, accumulating evidence has demonstrated a crucial role of the dopamine system in regulating several brain diseases, especially drug addiction, Parkinson's disorder, schizophrenia, anxiety, and depression [16]. The signal of dopamine is mediated by dopamine receptors and several downstream messengers, such as protein kinase A, protein kinase C, extracellular signal-regulated kinase, Ca 2+ /calmodulin-dependent kinase II, and DARPP-32 [14,17,18]. Among them, DARPP-32, which is enriched in the dopamine-innervated brain areas, could be a promising candidate for treating drug addiction [15].…”

Section: Dopaminergic Systemmentioning

confidence: 99%

Drug addiction: a curable mental disorder?

Liu

2018

Acta Pharmacol Sin

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Drug addiction is a chronic, relapsing brain disorder. Multiple neural networks in the brain including the reward system (e.g., the mesocorticolimbic system), the anti-reward/stress system (e.g., the extended amygdala), and the central immune system, are involved in the development of drug addiction and relapse after withdrawal from drugs of abuse. Preclinical and clinical studies have demonstrated that it is promising to control drug addiction by pharmacologically targeting the addiction-related systems in the brain. Here we review the pharmacological targets within the dopamine system, glutamate system, trace amine system, antireward system, and central immune system, which are of clinical interests. Furthermore, we discuss other potential therapies, e.g., brain stimulation, behavioral treatments, and therapeutic gene modulation, which could be effective to treat drug addiction. We conclude that, although drug addiction is a complex disorder that involves complicated neural mechanisms and psychological processes, this mental disorder is treatable and may be curable by therapies such as gene modulation in the future.

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Extracellular Signal-Regulated Kinase in Nucleus Accumbens Mediates Propofol Self-Administration in Rats

Cited by 29 publications

References 37 publications

Up-regulation of CXCR4 expression contributes to persistent abdominal pain in rats with chronic pancreatitis

Up-regulation of CXCR4 expression contributes to persistent abdominal pain in rats with chronic pancreatitis

The Role of NMDA receptors in rat propofol self-administration

Drug addiction: a curable mental disorder?

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