The pharmacology of the spinal receptor systems controlling the micturition reflex in the unanesthetized-intact and spinal-traumatized preparations have not been studied. We have developed a preparation whereby drugs may be easily and atraumatically administered intrathecally in the unanesthetized cat and the spinal effects of receptor active agents studied. The effect of activating specific spinal receptor systems on the volume evoked micturition reflex (VEM) in the unanesthetized cat is studied by means of cystometrograms carried out with an externalized catheter permanently placed through the vertex of the bladder. Based on preliminary experiments, opiate (morphine), Alpha2 (ST-91), dopamine (apomorphine) receptor selective agonists have an inhibitory effect on the VEM. In each case, the appropriate intrathecal antagonist (naloxone, yohimbine and fluphenthixol) reversed the inhibition. We have further developed this preparation such that local administration of agents can be made selectively in the unanesthetized animal at the level of the thoracic (sympathetic) and sacral (parasympathetic) cord. Preliminary experiments suggest that Alpha2 agonists may inhibit bladder function at the level of the sacral cord, but facilitate the reflx at the thoracic level. In addition, in defining the role of the several pharmacologically defined receptor systems acting at the level of the sympathetic and parasympathetic outflow in the normal animal, we will examine the role of these spinal receptor systems in the atonic and areflexic bladder which occurs during the period 7-40 days postspinal transection and in the subsequent state when the autonomous cord bladder develops. The mechanisms behind these altered states of bladder reactivity have not been satisfactorily explained other than the mechanistic idea that it is a loss of facilitation generated by a spinobulbospinal pathway. The present experiments carried out with focally administered receptor-selective-antagonists in the intact and spinally transected preparation will serve not only to define the specificity of the interaction between the intrathecal agonist and the spinal receptor, but the ongoing role of that receptor in the systems which are naturally activated during the VEM in the normal and postspinal transected animal.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS019650-03
Application #
3399770
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1983-07-01
Project End
1986-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
City
Rochester
State
MN
Country
United States
Zip Code
55905