Skip to Content
MilliporeSigma
  • Enhancing depression mechanisms in midbrain dopamine neurons achieves homeostatic resilience.

Enhancing depression mechanisms in midbrain dopamine neurons achieves homeostatic resilience.

Science (New York, N.Y.) (2014-04-20)
Allyson K Friedman, Jessica J Walsh, Barbara Juarez, Stacy M Ku, Dipesh Chaudhury, Jing Wang, Xianting Li, David M Dietz, Nina Pan, Vincent F Vialou, Rachael L Neve, Zhenyu Yue, Ming-Hu Han
ABSTRACT

Typical therapies try to reverse pathogenic mechanisms. Here, we describe treatment effects achieved by enhancing depression-causing mechanisms in ventral tegmental area (VTA) dopamine (DA) neurons. In a social defeat stress model of depression, depressed (susceptible) mice display hyperactivity of VTA DA neurons, caused by an up-regulated hyperpolarization-activated current (I(h)). Mice resilient to social defeat stress, however, exhibit stable normal firing of these neurons. Unexpectedly, resilient mice had an even larger I(h), which was observed in parallel with increased potassium (K(+)) channel currents. Experimentally further enhancing Ih or optogenetically increasing the hyperactivity of VTA DA neurons in susceptible mice completely reversed depression-related behaviors, an antidepressant effect achieved through resilience-like, projection-specific homeostatic plasticity. These results indicate a potential therapeutic path of promoting natural resilience for depression treatment.

MATERIALS
Product Number
Brand
Product Description

Supelco
Lamotrigine solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®
Lamotrigine for system suitability, European Pharmacopoeia (EP) Reference Standard
Lamotrigine for peak identification, European Pharmacopoeia (EP) Reference Standard
Lamotrigine, European Pharmacopoeia (EP) Reference Standard
USP
Lamotrigine, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Lamotrigine, ≥98%, powder
Supelco
Lamotrigine, Pharmaceutical Secondary Standard; Certified Reference Material