| First Author | Bruchas MR | Year | 2011 |
| Journal | Neuron | Volume | 71 |
| Issue | 3 | Pages | 498-511 |
| PubMed ID | 21835346 | Mgi Jnum | J:174677 |
| Mgi Id | MGI:5140620 | Doi | 10.1016/j.neuron.2011.06.011 |
| Citation | Bruchas MR, et al. (2011) Selective p38alpha MAPK Deletion in Serotonergic Neurons Produces Stress Resilience in Models of Depression and Addiction. Neuron 71(3):498-511 |
| abstractText | Maladaptive responses to stress adversely affect human behavior, yet the signaling mechanisms underlying stress-responsive behaviors remain poorly understood. Using a conditional gene knockout approach, the alpha isoform of p38 mitogen-activated protein kinase (MAPK) was selectively inactivated by AAV1-Cre-recombinase infection in specific brain regions or by promoter-driven excision of p38alpha MAPK in serotonergic neurons (by Slc6a4-Cre or ePet1-Cre) or astrocytes (by Gfap-CreERT2). Social defeat stress produced social avoidance (a model of depression-like behaviors) and reinstatement of cocaine preference (a measure of addiction risk) in wild-type mice, but not in mice having p38alpha MAPK selectively deleted in serotonin-producing neurons of the dorsal raphe nucleus. Stress-induced activation of p38alpha MAPK translocated the serotonin transporter to the plasma membrane and increased the rate of transmitter uptake at serotonergic nerve terminals. These findings suggest that stress initiates a cascade of molecular and cellular events in which p38alpha MAPK induces a hyposerotonergic state underlying depression-like and drug-seeking behaviors. |
