Opioid μ receptor activation inhibits sodium currents in prefrontal cortical neurons via a protein kinase A- and C-dependent mechanism

Witkowski, Grzegorz; Szulczyk, Paweł

doi:10.1016/j.brainres.2006.03.119

Cited by 39 publications

(36 citation statements)

References 58 publications

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“…Endogenous opioid peptides (present in the PFC as enkephalin (ENK), β-endorphin, and endomorphins; Ferezou et al (2007) and Martin-Schild et al (1999)) act upon μORs at key points within the PFC cellular network. PFC μORs are localized on GABA interneurons (not pyramidal cells) (Ferezou et al, 2007;Taki et al, 2000), and endogenous ENK acts at these receptors to suppress interneuron activity and to reduce inhibitory currents onto pyramidal cells (Ferezou et al, 2007;Witkowski and Szulczyk, 2006). This action removes an inhibitory component from cellular network function, presumably disinhibiting the network in a manner similar to μ-opioid actions in the hippocampus (McQuiston and Saggau, 2003).…”

Section: Discussionmentioning

confidence: 99%

Endogenous Opioid Signaling in the Medial Prefrontal Cortex is Required for the Expression of Hunger-Induced Impulsive Action

Selleck

Lake

Estrada

et al. 2015

Neuropsychopharmacol

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Opioid transmission and dysregulated prefrontal cortex (PFC) activity have both been implicated in the inhibitory-control deficits associated with addiction and binge-type eating disorders. What remains unknown, however, is whether endogenous opioid transmission within the PFC modulates inhibitory control. Here, we compared intra-PFC opioid manipulations with a monoamine manipulation (d-amphetamine), in two sucrose-reinforced tasks: progressive ratio (PR), which assays the motivational value of an incentive, and differential reinforcement of low response rates (DRLs), a test of inhibitory control. Intra-PFC methylnaloxonium (M-NX, a limited diffusion opioid antagonist) was given to rats in a 'low-drive' condition (2-h food deprivation), and also after a motivational shift to a 'highdrive' condition (18-h food deprivation). Intra-PFC DAMGO (D-[Ala2,N-MePhe4, Gly-ol]-enkephalin; a μ-opioid agonist) and damphetamine were also tested in both tasks, under the low-drive condition. Intra-PFC M-NX nearly eliminated impulsive action in DRL engendered by hunger, at a dose (1 μg) that significantly affected neither hunger-induced PR enhancement nor hyperactivity. At a higher dose (3 μg), M-NX eliminated impulsive action and returned PR breakpoint to low-drive levels. Conversely, intra-PFC DAMGO engendered 'high-drive-like' effects: enhancement of PR and impairment of DRL performance. Intra-PFC d-amphetamine failed to produce effects in either task. These results establish that endogenous PFC opioid transmission is both necessary and sufficient for the expression of impulsive action in a high-arousal, high-drive appetitive state, and that PFC-based opioid systems enact functionally unique effects on food impulsivity and motivation relative to PFC-based monoamine systems. Opioid antagonists may represent effective treatments for a range of psychiatric disorders with impulsivity features.

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Section: Discussionmentioning

confidence: 99%

Endogenous Opioid Signaling in the Medial Prefrontal Cortex is Required for the Expression of Hunger-Induced Impulsive Action

Selleck

Lake

Estrada

et al. 2015

Neuropsychopharmacol

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“…The same modulator can also act through different signaling pathways. Dopamine, for instance, acts through different second messenger systems that synergistically modulate Ca 2+ currents in teleost retinal horizontal cells [83], and the same is true for μ-opioid receptor mediated modulation of Na + channels in the prefrontal cortex, which depends on both PKA and PKC [84]. …”

Section: Neuromodulation Of Neuronal Excitabilitymentioning

confidence: 99%

Neuromodulation of neurons and synapses

Nadim

Bucher

2014

Current Opinion in Neurobiology

269

230

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Neuromodulation underlies the flexibility of neural circuit operation and behavior. Individual neuromodulators can have divergent actions in a neuron by targeting multiple physiological mechanisms. Conversely, multiple neuromodulators may have convergent actions through overlapping targets. Additionally, the divergent and convergent neuromodulator actions can be unambiguously synergistic or antagonistic. Neuromodulation often entails balanced adjustment of nonlinear membrane and synaptic properties by targeting ion channel and synaptic dynamics rather than just excitability or synaptic strength. In addition, neuromodulators can exert effects at multiple timescales, from short-term adjustments of neuron and synapse function to persistent long-term regulation. This short review summarizes some highlights of the diverse actions of neuromodulators on ion channel and synaptic properties.

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“…Opioid receptors are members of the G-protein-coupled receptor superfamily [76], and can functionally couple with ion channels, including Na + channels [16, 17, 77]. Our previous data implied an interaction between opioid receptors and Na + channels.…”

Section: Potential Mechanisms Of Acupuncture Inhibition Of Neuronamentioning

confidence: 99%

“…For example, in acutely isolated cortical neurons, the application of 1 μ M of DAMGO, a specific MOR agonist, caused a decrease in the Na + current amplitude to approximately 79% of the controls. Moreover, DAMGO decreased the maximum current activation rate, prolonged its time-dependent inactivation, shifted the half inactivation voltage from −63.4 mV to −71.5 mV, and prolonged the time constant of recovery from inactivation from 5.4 ms to 7.4 ms [77]. DAMGO also inhibited TTX-resistant voltage-dependent Na + current in dorsal root ganglion neurons [82].…”

Section: Potential Mechanisms Of Acupuncture Inhibition Of Neuronamentioning

confidence: 99%

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From Acupuncture to Interaction betweenδ-Opioid Receptors and Na⁺Channels: A Potential Pathway to Inhibit Epileptic Hyperexcitability

Chao

Shen

Xia

2013

Evidence-Based Complementary and Alternative Medicine

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Epilepsy is one of the most common neurological disorders affecting about 1% of population. Although the precise mechanism of its pathophysiological changes in the brain is unknown, epilepsy has been recognized as a disorder of brain excitability characterized by recurrent unprovoked seizures that result from the abnormal, excessive, and synchronous activity of clusters of nerve cells in the brain. Currently available therapies, including medical, surgical, and other strategies, such as ketogenic diet and vagus nerve stimulation, are symptomatic with their own limitations and complications. Seeking new strategies to cure this serious disorder still poses a big challenge to the field of medicine. Our recent studies suggest that acupuncture may exert its antiepileptic effects by normalizing the disrupted neuronal and network excitability through several mechanisms, including lowering the overexcited neuronal activity, enhancing the inhibitory system, and attenuating the excitatory system in the brain via regulation of the interaction between δ-opioid receptors (DOR) and Na+ channels. This paper reviews the progress in this field and summarizes new knowledge based on our work and those of others.

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Opioid μ receptor activation inhibits sodium currents in prefrontal cortical neurons via a protein kinase A- and C-dependent mechanism

Cited by 39 publications

References 58 publications

Endogenous Opioid Signaling in the Medial Prefrontal Cortex is Required for the Expression of Hunger-Induced Impulsive Action

Endogenous Opioid Signaling in the Medial Prefrontal Cortex is Required for the Expression of Hunger-Induced Impulsive Action

Neuromodulation of neurons and synapses

From Acupuncture to Interaction betweenδ-Opioid Receptors and Na⁺Channels: A Potential Pathway to Inhibit Epileptic Hyperexcitability

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Opioid μ receptor activation inhibits sodium currents in prefrontal cortical neurons via a protein kinase A- and C-dependent mechanism

Cited by 39 publications

References 58 publications

Endogenous Opioid Signaling in the Medial Prefrontal Cortex is Required for the Expression of Hunger-Induced Impulsive Action

Endogenous Opioid Signaling in the Medial Prefrontal Cortex is Required for the Expression of Hunger-Induced Impulsive Action

Neuromodulation of neurons and synapses

From Acupuncture to Interaction betweenδ-Opioid Receptors and Na+Channels: A Potential Pathway to Inhibit Epileptic Hyperexcitability

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From Acupuncture to Interaction betweenδ-Opioid Receptors and Na⁺Channels: A Potential Pathway to Inhibit Epileptic Hyperexcitability