| First Author | Burke TF | Year | 2013 |
| Journal | Int J Neuropsychopharmacol | Volume | 16 |
| Issue | 3 | Pages | 631-45 |
| PubMed ID | 22575584 | Mgi Jnum | J:329585 |
| Mgi Id | MGI:6879705 | Doi | 10.1017/S1461145712000466 |
| Citation | Burke TF, et al. (2013) Sensitivity of hippocampal 5-HT1A receptors to mild stress in BDNF-deficient mice. Int J Neuropsychopharmacol 16(3):631-45 |
| abstractText | Serotonin 1A (5-HT(1A)) receptors in brain play an important role in cognitive and integrative functions, as well as emotional states. Decreased brain-derived neurotrophic factor (BDNF) expression and/or function, particularly in hippocampus, are implicated in the pathophysiology of stress-related disorders such as major depression. BDNF(+/-) mice are more vulnerable to stress than wild-type mice, exhibiting behavioural despair after mild handling stress. We examined the effect of mild handling stress on 5-HT(1A) receptor function, as measured by 8-OH-DPAT stimulated [(35)S]GTPgammaS binding, in BDNF(+/-) mice and mice with a forebrain-specific reduction in BDNF (embryonic BDNF inducible knockout mice). Our data show a remarkable sensitivity of hippocampal 5-HT1A receptors to mild stress and a deficiency in BDNF. Other 5-HT(1A) receptor populations, specifically in frontal cortex and dorsal raphe, were resistant to the combined detrimental effects of mild stress and reductions in BDNF expression. Decreases in hippocampal 5-HT(1A) receptor function induced by mild stress in BDNF-deficient mice were prevented by administration of the selective serotonin reuptake inhibitor fluoxetine, which increased activation of TrkB, the high affinity receptor for BDNF, in wild-type and BDNF(+/-) mice. In hippocampal cultures, BDNF increased the capacity of 5-HT(1A) receptors to activate G proteins, an effect eliminated by the knockout of TrkB, confirming TrkB activation increases 5-HT(1A) receptor function. The mechanisms underlying the sensitivity of hippocampal 5-HT(1A) receptors to mild stress and decreased BDNF expression remain to be elucidated and may have important implications for the emotional and cognitive impairments associated with stress-related mental illness. |
