title: GABAergic control of micturition within the periaqueductal grey matter of the male rat.
abstract: In urethane-anaesthetised rats continuous infusion of saline into the bladder (6 ml h⁻¹) evoked periodic sharp rises in intravesicular pressure accompanied by rhythmic bursting of external urethral sphincter (EUS) EMG and expulsion of urine from the urethral meatus. Microinjection of the GABA agonist muscimol (250 pmol) into the caudal ventrolateral periaqueductal grey (PAG), but not at other sites in the PAG, either depressed reflex voiding frequency (-60%, n = 7) and tonic EUS EMG activity (-38%, n = 6) or completely inhibited voiding (four sites). Microinjection of the GABA antagonist bicuculline (BIC; 1 nmol) into the same region, to reduce ongoing GABA tone, increased reflex voiding frequency (+467%, n = 16) and tonic activity in the EUS (+56%, n = 7) whilst bursting activity in the EUS became desynchronised. Although muscimol failed to change reflex micturition when microinjected into the dorsal caudal PAG, microinjection of BIC at these sites evoked pronounced autonomic arousal and increased reflex voiding frequency (+237%, n = 34). The results demonstrate that the functional integrity of synapses in the caudal ventrolateral PAG is essential to permit micturition. Transmission through the region is normally regulated by a tonic GABAergic inhibitory influence. In contrast, the functional integrity of the dorsal caudal PAG is not essential for reflex micturition. However, micturition may be initiated from this region via projections to the caudal ventrolateral PAG, as part of the behavioural response to psychological threat or other stressful stimuli.
authors.affiliation: School of Clinical and Experimental Medicine, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: E
authors.initials: E
authors.lastname: Stone
authors.forename: J H
authors.initials: JH
authors.lastname: Coote
authors.forename: J
authors.initials: J
authors.lastname: Allard
authors.forename: T A
authors.initials: TA
authors.lastname: Lovick
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D004576:Electromyography; D058785:GABA-A Receptor Agonists / Q000008:administration & dosage; D058787:GABA-A Receptor Antagonists / Q000008:administration & dosage; D007263:Infusions, Parenteral; D008297:Male; D008845:Microinjections; D009433:Neural Inhibition; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism*; D010487:Periaqueductal Gray / Q000187:drug effects / Q000378:metabolism*; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects; D012965:Sodium Chloride / Q000008:administration & dosage; D009435:Synaptic Transmission; D013997:Time Factors; D001743:Urinary Bladder / Q000294:innervation*; D014554:Urination / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D012965:Sodium Chloride; D005680:gamma-Aminobutyric Acid