The long range objective is to understand how bulbospinal serotonergic neurons regulate sensory input. This understanding is sought in terms of the specific mechanisms by which this system regulates motor reflexes and pain perception. In addition, specific sites for pharmacological attack on the serotonergic regulation of sensory perception will be defined. The initial goal is to determine how serotonin (5-HT) directly affects primary afferent transmission. This understanding is sought both in terms of the characteristics of the membrane receptors on which 5-HT acts, as well as the neuronal sites and membrane permeability changes by which the effect is mediated. The initial approach will use intracellular recording from primary afferent cell bodies to study the membrane effects of directly applied 5-HT. The receptors mediating these effects will be characterized by their agonist and antagonist selectivity defined using dose-response criteria. The presence of receptor coupling to the adenylate cyclase system will be explored. With the pharmacological probes, defined in the above experiments, the effects of 5-HT on primary afferent transmission will be pursued in the isolated hemisected frog spinal cord and the in vivo rat spinal cord. Changes in the size of the excitatory post synaptic potential (EPSP) will be used as an index of the presynaptic action of the 5-HT agonists. From these data, mechanisms for 5-HT modulation of pre-synaptic modulation should emerge. We have observed that various primary afferent cell bodies exhibit differing spectra of membrane responses to 5-HT and the sensory modality of the cell will be investigated in situ. An intact rat preparation will be used where intracellular recordings from DRG cells still connected with their peripheral receptors can be made. The sensory modality of the peripheral receptors can then be compared with the nature of the membrane responses to 5-HT. From these observations we can determine if 5-HT selectively inhibits and/or facilitates specific sensory modalities.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS017834-01A2
Application #
3397871
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1985-09-09
Project End
1988-08-31
Budget Start
1985-09-09
Budget End
1986-08-31
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Illinois at Chicago
Department
Type
Overall Medical
DUNS #
121911077
City
Chicago
State
IL
Country
United States
Zip Code
60612
Glaum, S R; Proudfit, H K; Anderson, E G (1990) 5-HT3 receptors modulate spinal nociceptive reflexes. Brain Res 510:12-6
Glaum, S R; Anderson, E G (1988) Identification of 5-HT3 binding sites in rat spinal cord synaptosomal membranes. Eur J Pharmacol 156:287-90
Glaum, S R; Proudfit, H K; Anderson, E G (1988) Reversal of the antinociceptive effects of intrathecally administered serotonin in the rat by a selective 5-HT3 receptor antagonist. Neurosci Lett 95:313-7