The effects of baclofen on spinal and supraspinal micturition reflexes in rats

Publisher Website
Google Scholar
Abstract
Summary 1. The effect of (±)-baclofen on micturition reflexes was investigated in urethane-anaesthetized rats. A ‘low’ dose of (±)-baclofen (0.5 mg/kg i.v.) barely affected the early phase of the transurethral cystometrogram (CMG) which involves activation of a spinal vesico-vesical excitatory reflex. 2. At a higher dose (2.5 mg/kg i.v.) (±)-baclofen suppressed both the spinal and supraspinal components of the bladder response to transurethral saline filling. 3. When the bladder was filled by the transvesical route a series of regular voiding cycles was obtained which are due to activation of a supraspinal vesico-vesical excitatory reflex. In this model, voiding efficiency of the rat bladder was markedly reduced even after a low dose of (±)-baclofen (0.5 mg/kg) and almost suppressed at 2.5 mg/kg. 4. (±)-Baclofen reduction of voiding efficiency was mainly ascribable to an inhibitory effect on the expulsive phase of the voiding cycle which, in rats, depends critically upon the activation of a reflex which induces a twitch-like contraction of urethral/periurethral skeletal muscles. 5. (±)-Baclofen produced a small inhibition of the pinching-induced somatovesical excitatory reflex. (±)-Baclofen (2.5 mg/kg i.v.) produced also a marked but transient inhibition of bladder contractions induced by preganglionic nerve stimulation. However the time course of this effect was markedly shorter as compared to the long lasting suppression of voiding cycle observed with this same dose of the drug. 6. (−)-Baclofen, which is more potent than (±)-baclofen as a GABA B receptor agonist, affected bladder response to transurethral or transvesical filling in a manner similar to that observed with the racemate, but at lower doses (0.1–0.5 mg/kg i.v.). 7. These findings indicate that: a) (±)-baclofen affects markedly various types of reflexes concerned with micturition; b) a central site seems the main determinant of its action; c) at a low dose level inhibition of the reflex activation of urethral/periurethral skeletal muscles rather than the detrusor is a main target for (±)-baclofen action and d) GABA B receptors may modulate excitatory neurotransmission in rat pelvic ganglia.