Suppression of bladder reflex activity in chronic spinal cord injured cats by activation of serotonin 5-HT1A receptors.
The effects of 8-OH-DPAT (5-HT1A receptor agonist) and WAY100635 (5-HT1A receptor antagonist) on reflex bladder activity were investigated in alpha-chloralose anesthetized or conscious chronic spinal cord injured cats. The results were similar in both anesthetized and conscious animals. Cystometrograms revealed that 8-OH-DPAT (0.5 mg/kg, s.c.) significantly increased the bladder volume threshold for eliciting a large amplitude micturition contraction, but only slightly reduced the amplitude of the contractions and did not alter the small amplitude pre-micturition contractions. 8-OH-DPAT also reduced the amplitude of isovolumetric bladder contractions. The inhibitory effect of 8-OH-DPAT was reversed by WAY100635 (0.5 mg/kg) or blocked by pre-treatment with WAY100635. Reflex bladder contractions evoked by tactile stimulation of the perigenital region were not altered by 8-OH-DPAT. These results suggest that the inhibitory effect of 8-OH-DPAT is mediated by an action on interneuronal pathways in the spinal cord or on the C-fiber afferent limb of the spinal micturition reflex and not on bladder smooth muscle or the efferent limb of the reflex pathway. Drugs that activate 5-HT1A receptors might be useful in treating detrusor overactivity after spinal cord injury.
Department of Pharmacology, University of Pittsburgh, W1354 Biomedical Science Tower, Pittsburgh, PA 15261, USA. cftai@pitt.edu
Changfeng
C
Tai
Cynthia L
CL
Miscik
Timothy D
TD
Ungerer
James R
JR
Roppolo
William C
WC
de Groat
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D002415:Cats; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D012018:Reflex / Q000187:drug effects / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D001743:Urinary Bladder / Q000187:drug effects / Q000503:physiopathology*; D014851:Wakefulness
D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin