| First Author | Sambo DO | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Issue | 1 | Pages | 2228 |
| PubMed ID | 29263318 | Mgi Jnum | J:256524 |
| Mgi Id | MGI:6112375 | Doi | 10.1038/s41467-017-02087-x |
| Citation | Sambo DO, et al. (2017) The sigma-1 receptor modulates methamphetamine dysregulation of dopamine neurotransmission. Nat Commun 8(1):2228 |
| abstractText | Dopamine neurotransmission is highly dysregulated by the psychostimulant methamphetamine, a substrate for the dopamine transporter (DAT). Through interactions with DAT, methamphetamine increases extracellular dopamine levels in the brain, leading to its rewarding and addictive properties. Methamphetamine also interacts with the sigma-1 receptor (sigma1R), an inter-organelle signaling modulator. Using complementary strategies, we identified a novel mechanism for sigma1R regulation of dopamine neurotransmission in response to methamphetamine. We found that sigma1R activation prevents methamphetamine-induced, DAT-mediated increases in firing activity of dopamine neurons. In vitro and in vivo amperometric measurements revealed that sigma1R activation decreases methamphetamine-stimulated dopamine efflux without affecting basal dopamine neurotransmission. Consistent with these findings, sigma1R activation decreases methamphetamine-induced locomotion, motivated behavior, and enhancement of brain reward function. Notably, we revealed that the sigma1R interacts with DAT at or near the plasma membrane and decreases methamphetamine-induced Ca(2+) signaling, providing potential mechanisms. Broadly, these data provide evidence for sigma1R regulation of dopamine neurotransmission and support the sigma1R as a putative target for the treatment of methamphetamine addiction. |
