Serotonergic receptors are the focus of the proposed studies since alterations in this neurotransmitter system have been implicated in the etiology of age-related diseases, including anxiety and clinical depression. The 5-HT1A receptor has been chosen for examination as it has been implicated in each of these disorders. The pattern of age-related changes in 5-HT1A receptor function will be investigated using an appropriate model, male Fischer 344 rats (ages 3, 14 and 24 mo). The overall goal is to test the hypothesis that the functional dynamics of 5-HT1A receptors are significantly compromised with aging.
The specific aims of this project include evaluation of age- related alterations in the: l) neuroanatomical, functional and molecular representation of the 5-HT1A receptor using radioligand binding, quantitative autoradiograph, and in situ hybridization techniques, 2) physiological responses of 5-HT1A receptors using in vivo and in vitro electrophysiological recording preparations and 3) neurochemical and physiological characterization of 5-HT1A spare receptor pools following 1-ethoxycarbonyl-2-ethoxy-1,2- dihydroquinoline (EEDQ) treatment. These data will provide the foundation for a better understanding of the neurochemical basis of behavioral processes mediated by serotonin in the elderly patient. Ultimately, this research will contribute new information for the development of more effective treatments for the management of depression and anxiety in the elderly.
| Keck, B J; Lakoski, J M (2000) Regional heterogeneity of serotonin(1A) receptor inactivation and turnover in the aging female rat brain following EEDQ. Neuropharmacology 39:1237-46 |
| Maines, L W; Keck, B J; Dugar, A et al. (1998) Age-dependent loss of corticosterone modulation of central serotonin 5-HT1A receptor binding sites. J Neurosci Res 53:86-98 |
| Keck, B J; Lakoski, J M (1997) N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) administration for studies of 5-HT1A receptor binding site inactivation and turnover. Brain Res Brain Res Protoc 1:364-70 |
| Keck, B J; Lakoski, J M (1996) Region-specific serotonin1A receptor turnover following irreversible blockade with EEDQ. Neuroreport 7:2717-21 |
