Proceedings of The Physiological Society

University College Dublin (2009) Proc Physiol Soc 15, C100

Oral Communications

Midbrain control of micturition in the rat

E. Stone1, J. H. Coote1, J. Allard2, T. A. Lovick1

1. University of Birmingham, Birmingham, United Kingdom. 2. Pfizer Ltd, Sandwich, United Kingdom.

In most socialised animals voiding can be suppressed, even when the bladder is full, until the individual is in a safe and socially acceptable environment. In the rat, stimulation of bladder afferents during filling activates a spino-midbrain-spinal micturition reflex pathway that relays in the periaqueductal grey (PAG) (DeGroat, 2006). We have investigated whether the synaptic relay in the PAG could be a site of tonic inhibitory control over micturition. Urethane anaesthetised (1.5g/Kg i.p.) male Sprague-Dawley rats were instrumented to record femoral arterial pressure, heart rate and tracheal airflow. A cannula inserted through the dome was used to measure intravesicular pressure and for infusion of saline (6ml h-1) to induce periodic (0.6±0.05 min-1, mean ± S.E.M.) increases in bladder pressure, accompanied by expulsion of urine through the urethra. The GABA agonist muscimol (250pmol in 50nl) microinjected into the caudal ventrolateral PAG (vlPAG, P-8.8 Paxinos & Watson, 1986, n=3), but not at other sites in the PAG (n=16) completely suppressed the periodic contractions. Microinjection of the GABAA antagonist bicuculline (1pmol in 50nl) into the caudal vlPAG (n=13) evoked an increase in the frequency (from 0.7±0.1 to 2.3±0.4min-1, P < 0.05, Student’s paired t-test) and threshold (14.5±1.0 to 20.6±2.0 mmHg, P< 0.05) of contraction that lasted 1106±253s (range 263s-2911s). At 8/13 (68.5%) sites this effect was accompanied by a pressor response (mean arterial pressure 86.9±4.6 to 123.9±8.5 mmHg, P< 0.01), which lasted 1680±253s (range 780s-2718s), tachypnoea (158.8±5.6 to 323.1±45.9 breaths min-1, P < 0.05), exopthalmus and pupillary dilatation. At the remaining sites (n=5) there were no accompanying cardio-respiratory changes. In contrast, bicuculline microinjected at more dorsal sites in the caudal PAG (n=14) evoked a long lasting (>60min) irreversible increase in bladder pressure (16.2±0.8 to 25.9±1.9mm Hg, P < 0.01) on top of which frequent (3.1±0.5 min-1) low amplitude contractions were superimposed. These changes in bladder activity were accompanied by a sustained pressor response (88.1±3.1 to 139.1±5.6mmHg, P< 0.01), tachycardia (438.4±12.6 to 547.4±41.0 beats min-1, P< 0.01), increases in respiratory amplitude (128.1±16.7 to 316.7±44.3, arbitrary units P < 0.01) and respiratory rate (164.7±5.1 to 318.6±22.3 breaths min-1, P < 0.01) and pronounced signs of autonomic activation (exopthalmus and pupillary dilatation). The results suggest i) the functional integrity of the caudal vlPAG is necessary for reflex micturition to occur in response to bladder filling and ii) the synaptic relays in this region are under tonic GABAergic control. In addition, the dorsal PAG, whilst not essential for execution of the reflex, can facilitate contractile activity of the bladder in concert with intense sympatho-activation.

Where applicable, experiments conform with Society ethical requirements