Maturational alterations in constitutive activity of medial prefrontal cortex kappa-opioid receptors in Wistar rats

Sunil Sirohi; Brendan M Walker

doi:10.1111/jnc.13279

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Maturational alterations in constitutive activity of medial prefrontal cortex kappa-opioid receptors in Wistar rats

Journal article

Open access

Peer reviewed

Maturational alterations in constitutive activity of medial prefrontal cortex kappa-opioid receptors in Wistar rats

Sunil Sirohi and Brendan M Walker

Journal of neurochemistry, Vol.135(4), pp.659-665

11/2015

DOI: https://doi.org/10.1111/jnc.13279

Handle:

https://hdl.handle.net/2376/113160

PMCID: PMC4636924

PMID: 26257334

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Abstract

Naltrexone - analogs & derivatives

Somatostatin - analogs & derivatives

Age Factors

Rats, Wistar

Enkephalin, Ala-MePhe-Gly- - pharmacology

Receptors, Opioid, kappa - metabolism

Analgesics, Opioid - pharmacology

Rats

Male

Prefrontal Cortex - growth & development

Sulfur Isotopes - pharmacokinetics

Somatostatin - pharmacology

Dose-Response Relationship, Drug

Naltrexone - pharmacology

Animals

Prefrontal Cortex - drug effects

Narcotic Antagonists - pharmacology

Protein Binding - drug effects

Prefrontal Cortex - metabolism

Radionuclide Imaging

Guanosine 5'-O-(3-Thiotriphosphate) - pharmacokinetics

Prefrontal Cortex - diagnostic imaging

Opioid receptors can display spontaneous agonist-independent G-protein signaling (basal signaling/constitutive activity). While constitutive κ-opioid receptor (KOR) activity has been documented in vitro, it remains unknown if KORs are constitutively active in native systems. Using [(35) S] guanosine 5'-O-[gamma-thio] triphosphate coupling assay that measures receptor functional state, we identified the presence of medial prefrontal cortex KOR constitutive activity in young rats that declined with age. Furthermore, basal signaling showed an age-related decline and was insensitive to neutral opioid antagonist challenge. Collectively, the present data are first to demonstrate age-dependent alterations in the medial prefrontal cortex KOR constitutive activity in rats and changes in the constitutive activity of KORs can differentially impact KOR ligand efficacy. These data provide novel insights into the functional properties of the KOR system and warrant further consideration of KOR constitutive activity in normal and pathophysiological behavior. Opioid receptors exhibit agonist-independent constitutive activity; however, kappa-opioid receptor (KOR) constitutive activity has not been demonstrated in native systems. Our results confirm KOR constitutive activity in the medial prefrontal cortex (mPFC) that declines with age. With the ability to presynaptically inhibit multiple neurotransmitter systems in the mPFC, maturational or patho-logical alterations in constitutive activity could disrupt corticofugal glutamatergic pyramidal projection neurons mediating executive function. Regulation of KOR constitutive activity could serve as a therapeutic target to treat compromised executive function.

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Title: Maturational alterations in constitutive activity of medial prefrontal cortex kappa-opioid receptors in Wistar rats
Creators: Sunil Sirohi - Department of Integrative Physiology & Neuroscience, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA
Brendan M Walker - Translational Addiction Research Center, Washington State University, Pullman, Washington, USA
Publication Details: Journal of neurochemistry, Vol.135(4), pp.659-665
Academic Unit: Integrative Physiology and Neuroscience, Department of
Publisher: England
Grant note: R01AA020394 / NIAAA NIH HHS R01 AA020394 / NIAAA NIH HHS
Identifiers: 99900548386001842
Language: English
Resource Type: Journal article