Research Interests- Serotonin: Regulation of serotonin release, antidepressant drugs and opioid effects on serotonin
Research statement- We are studying the neurotransmitter serotonin. In particular, we are interested in its role in depression and the possibility that persistent changes in the regulation of serotonin release are involved in adaptation to prolonged stress. Using in vivo microdialysis for measurement of extracellular serotonin in the brain, we have studied the influence of synaptic inputs and antidepressant drugs on serotonin release. Drugs like Prozac that block serotonin reuptake are effective in treating depression, but recovery is often slow. Our results indicate that reuptake inhibitors produce an immediate small increase in extracellular serotonin which is enhanced after prolonged administration. We have suggested that antidepressant drug treatment alters the strength of synaptic connections that regulate serotonin neurons. Because little is known, we have investigated the role of the neurotransmitters that may be involved in regulating serotonin release.
We were particularly interested in studying glutamate because this neurotransmitter is involved in synaptic plasticity in other brain sites. We found that glutamate can strongly stimulate serotonin release through activation of NMDA and AMPA receptors. However, our results indicate that these receptors do not have a strong tonic influence on serotonin. In contrast, the neurotransmitter GABA strongly inhibits serotonin release in vivo. Furthermore, our results indicate that opioids inhibit GABA release. Thus, endogenous opioids and opiate drugs such as morphine may indirectly stimulate serotonin release as a result of inhibiting GABA. However, after prolonged exposure, serotonin neurons become tolerant to the stimulatory effect of morphine, and serotonin release is inhibited during opiate withdrawal. We are currently investigating the cellular mechanisms that could be involved in this change and thus play a role in adaptation to prolonged stress as well as addiction to opiate drugs.
Representative Publications:
Tao, R. and Auerbach, S.B. Differential effect of NMDA on extracellular
serotonin in rat midbrain raphe and forebrain sites. J. Neurochem.,
1996, 66:1067-1075.
Tao, R., Ma, Z. and Auerbach, S.B. Differential regulation of 5-hydroxytryptamine release by GABAA and GABAB receptors in midbrain raphe nuclei and forebrain of rats. Br. J. Pharmacol., 1996, 119:1375-1384.
Tao, R., Ma, Z. and Auerbach, S.B. Influence of AMPA/kainate receptors on extracellular 5-hydroxytryptamine in rat midbrain raphe and forebrain. Br. J. Pharmacol., 1997, 121:1707-1715.
Tao, R., Ma, Z. and Auerbach, S.B. Alteration in regulation of serotonin release in rat dorsal raphe nucleus after prolonged exposure to morphine. J.Pharm. Exp. Ther., 1998, 286:481-488.
Auerbach, S.B. and Hjorth, S. Autoreceptors still restrain the 5-HT-elevating
effect of citalopram after chronic treatment in anesthetized rats. Brain
Res., 1999, 224-228.
Courses:
01:146:245 Fundamentals of Neurobiology