STEP signaling pathway mediates psychomotor stimulation and morphine withdrawal symptoms, but not for reward, analgesia and tolerance
| Autor: | Hye Yeon Park, Myungchull Rhee, Takuya Murata, Jae-Ran Lee, Kyoung Shim Kim, Young Jun Kang, Yoon-Jung Kim, Hyun-Jun Lee, Dae Yeul Yu, Bong Hyun Chung, Yong-Hoon Kim, Jung Hwan Hwang, Chul-Ho Lee, Yoichi Gondo, Pyung Lim Han |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Agonist Male medicine.drug_class Clinical Biochemistry Drug Resistance Stimulation Pharmacology Biochemistry 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Reward Dopamine Opioid receptor medicine Animals Point Mutation Phosphorylation Receptor Molecular Biology Psychomotor Agitation Mice Knockout Morphine business.industry Protein Tyrosine Phosphatases Non-Receptor Corpus Striatum Substance Withdrawal Syndrome Analgesics Opioid DAMGO Disease Models Animal 030104 developmental biology Opioid chemistry Receptors Opioid Molecular Medicine Original Article Female Signal transduction Analgesia business 030217 neurology & neurosurgery medicine.drug Signal Transduction |
| Zdroj: | Experimental & Molecular Medicine |
| ISSN: | 2092-6413 1226-3613 |
| Popis: | Striatal-enriched protein tyrosine phosphatase (STEP) is abundantly expressed in the striatum, which strongly expresses dopamine and opioid receptors and mediates the effects of many drugs of abuse. However, little is known about the role of STEP in opioid receptor function. In the present study, we generated STEP-targeted mice carrying a nonsense mutation (C230X) in the kinase interaction domain of STEP by screening the N-ethyl-N-nitrosourea (ENU)-driven mutant mouse genomic DNA library and subsequent in vitro fertilization. It was confirmed that the C230X nonsense mutation completely abolished functional STEP protein expression in the brain. STEP(C230X-/-) mice showed attenuated acute morphine-induced psychomotor activity and withdrawal symptoms, whereas morphine-induced analgesia, tolerance and reward behaviors were unaffected. STEP(C230X-/-) mice displayed reduced hyperlocomotion in response to intrastriatal injection of the μ-opioid receptor agonist DAMGO, but the behavioral responses to δ- and κ-opioid receptor agonists remained intact. These results suggest that STEP has a key role in the regulation of psychomotor action and physical dependency to morphine. These data suggest that STEP inhibition may be a critical target for the treatment of withdrawal symptoms associated with morphine. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|