Specific behavioral and cellular adaptations induced by chronic morphine are reduced by dietary omega-3 polyunsaturated fatty acids
| Autor: | Camille Johnston, Ani Minasyan, Nicole Romaneschi, Joshua K. Hakimian, Fernando Gomez-Pinilla, Waleed Atallah, Wendy Walwyn, Alexander Vorperian, Austin Beltrand, Mariana Loureiro, Lily Zhe-Ying |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Physiology lcsh:Medicine Anxiety Euphoriant Running Mice 0302 clinical medicine Medicine and Health Sciences Receptor lcsh:Science chemistry.chemical_classification Analgesics Multidisciplinary Morphine Neuronal Morphology Pharmaceutics Drugs Brain Lipids 3. Good health Frontal Lobe Receptors Glutamate Dopamine receptor Female Opiate μ-opioid receptor Anatomy Locomotion Polyunsaturated fatty acid medicine.drug Research Article medicine.medical_specialty Motor Activity Real-Time Polymerase Chain Reaction Drug Administration Schedule 03 medical and health sciences Drug Therapy Internal medicine Fatty Acids Omega-3 medicine Pain Management Animals Maze Learning Nutrition Pharmacology business.industry Biological Locomotion lcsh:R Biology and Life Sciences Corpus Striatum Diet Opioids Neostriatum Mice Inbred C57BL 030104 developmental biology Endocrinology chemistry Opioid Cellular Neuroscience lcsh:Q Analgesia business 030217 neurology & neurosurgery Neuroscience |
| Zdroj: | PLoS ONE PLoS ONE, Vol 12, Iss 4, p e0175090 (2017) |
| ISSN: | 1932-6203 |
| Popis: | Opiates, one of the oldest known drugs, are the benchmark for treating pain. Regular opioid exposure also induces euphoria making these compounds addictive and often misused, as shown by the current epidemic of opioid abuse and overdose mortalities. In addition to the effect of opioids on their cognate receptors and signaling cascades, these compounds also induce multiple adaptations at cellular and behavioral levels. As omega-3 polyunsaturated fatty acids (n-3 PUFAs) play a ubiquitous role in behavioral and cellular processes, we proposed that supplemental n-3 PUFAs, enriched in docosahexanoic acid (DHA), could offset these adaptations following chronic opioid exposure. We used an 8 week regimen of n-3 PUFA supplementation followed by 8 days of morphine in the presence of this diet. We first assessed the effect of morphine in different behavioral measures and found that morphine increased anxiety and reduced wheel-running behavior. These effects were reduced by dietary n-3 PUFAs without affecting morphine-induced analgesia or hyperlocomotion, known effects of this opiate acting at mu opioid receptors. At the cellular level we found that morphine reduced striatal DHA content and that this was reversed by supplemental n-3 PUFAs. Chronic morphine also increased glutamatergic plasticity and the proportion of Grin2B-NMDARs in striatal projection neurons. This effect was similarly reversed by supplemental n-3 PUFAs. Gene analysis showed that supplemental PUFAs offset the effect of morphine on genes found in neurons of the dopamine receptor 2 (D2)-enriched indirect pathway but not of genes found in dopamine receptor 1(D1)-enriched direct-pathway neurons. Analysis of the D2 striatal connectome by a retrogradely transported pseudorabies virus showed that n-3 PUFA supplementation reversed the effect of chronic morphine on the innervation of D2 neurons by the dorsomedial prefontal and piriform cortices. Together these changes outline specific behavioral and cellular effects of morphine that can be reduced or reversed by dietary n-3 PUFAs. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|