Insulin enhances presynaptic glutamate release via opioid receptor-mediated disinhibition
| Autor: | Max F. Oginsky, Carrie R. Ferrario, Allison M. Nieto, Tracy L. Fetterly, Yanaira Alonso-Caraballo, Zuleirys Santana-Rodriguez |
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| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
medicine.medical_specialty biology Chemistry medicine.drug_class Insulin medicine.medical_treatment Glutamate receptor Nucleus accumbens 03 medical and health sciences Glutamatergic Insulin receptor 0302 clinical medicine Endocrinology Disinhibition Opioid receptor Internal medicine medicine biology.protein Cognitive decline medicine.symptom 030217 neurology & neurosurgery 030304 developmental biology |
| DOI: | 10.1101/517797 |
| Popis: | Insulin influences activity in brain centers that mediate reward and motivation in humans. However, nothing is known about how insulin influences excitatory transmission in regions like the nucleus accumbens (NAc), which governs motivational processes in the adult brain. Further, insulin dysregulation that accompanies obesity is linked to cognitive decline, depression, anxiety, and aberrant motivation that also rely on NAc excitatory transmission. Using a combination of whole-cell patch clamp and biochemical approaches we determined how insulin affects NAc glutamatergic transmission. We show that insulin receptor activation increases presynaptic glutamate release via a previously unidentified form of opioid receptor-mediated disinhibition. In contrast, activation of IGF receptors by insulin decreases presynaptic glutamate release in adult male rats. Furthermore, obesity results in a loss of insulin receptor-mediated increases and a reduction in NAc insulin receptor surface expression, while preserving reductions in transmission mediated by IGRFs. These results provide the first insights into how insulin influences excitatory transmission in the adult brain, they provide foundational information about opioid-mediated regulation of NAc glutamatergic transmission, and have broad implications for the regulation of motivation and reward related processes by peripheral hormones. |
| Databáze: | OpenAIRE |
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