Dr. Kirby’s research focuses on the effects of stress and stress hormones on the serotonin (5-HT) system. Serotonin is a brain neurotransmitter that is involved in a wide range of behaviors, including emotional behaviors. Long-term exposure to stress is known to play a role in psychiatric disorders such as anxiety and depression. Stress is also a potent initiator of relapse in abstinent subjects with a prior history of substance abuse. Some of these clinical effects of stress may in part be mediated by 5-HT. In the laboratory, we have examined the effects of stress and stress hormones on the electrical activity of 5-HT-containing cells in the brain and the release of 5-HT from nerve terminals.
We have found that stress has qualitatively different effects on 5-HT neurotransmission depending on the brain region examined and the particular stressor that is employed. We have also examined the role of 5-HT in anxiety using a knockout mouse model in which a particular 5-HT receptor subtype (5-HT 1A) has been removed from the brain, resulting in an anxious behavioral phenotype. Previous studies also included investigation of the effects of chemokine immune molecules in the brain and their interactions with traditional neurotransmitter (5-HT, dopamine) and neuropeptide (opiate) systems. Currently, we are examining the potential role that 5-HT circuits play in opiate and cocaine addiction and relapse. Through collaborations with other laboratories we are also exploring cannabinoid effects on cognition, synaptic plasticity and inflammation produced in a model of stroke.