GABAergic contribution to rat bladder hyperactivity after middle cerebral artery occlusion

Abstract

To evaluate the influences of gamma-aminobutyric acid (GABA) mechanisms on bladder hyperactivity after left middle cerebral artery occlusion, cystometric recordings were obtained from unanesthetized female rats. Intracerebroventricular administration of both muscimol (GABA(A) receptor agonist; 0.1-10 nmol) and baclofen (GABA(B) receptor agonist; 0.1-3 nmol) produced dose-dependent inhibitions of micturition with increases in bladder capacity (BC). The effects of high doses (1-10 nmol) were similar in sham-operated (SO) and cerebral-infarcted (CI) rats. However, lower doses of muscimol (0.1 or 0.3 nmol) and baclofen (0.1 nmol) reduced BC in CI rats. After bicuculline (GABA(A) receptor antagonist; 1 or 3 nmol) administration, BC in both SO and CI rats first decreased and subsequently increased. An increase in urethral pressure was observed after administration of bicuculline (3 nmol) but not with either muscimol or baclofen. Infarct volumes in muscimol-, bicuculline-, or baclofen-treated rats were not significantly different from those of vehicle-treated rats. These results suggest that GABAergic mechanisms inhibit the micturition reflex at the supraspinal level but that this can change as a result of CI.

Pathophysiology of overactive bladder

“…Various cortical lesions are thought to lead to these symptoms due to damage to the cerebral inhibitory centers leading to uninhibited detrusor contractions [26]. Other cerebral infarction-induced factors that may lead to OAB include alterations in N-methyl-D-aspartic acid glutamatergic mechanisms [27], dopamine D2 receptor excitatory mechanisms [28], dopaminergic-glutamatergic interactions in the brain [29], a central mechanism sensitive to nitric oxide [30], and a decreased GAGA-mediated inhibition of micturition [31]. Other neurological entities that are known to cause OAB syndrome include Parkinson's disease, multiple sclerosis, and spinal cord injuries.…”

Gene Expression Profiling of Mouse Bladder Inflammatory Responses to LPS, Substance P, and Antigen-Stimulation

“…These proteins and receptors may be involved in the regulation of nociceptive processing. Indeed, systemic or central administration of nociceptin, 28 enkephalins (intrathecal naloxone, 29 ), and GABA, 30 inhibits the micturition reflex. Interestingly, peripheral inflammation induces nociceptin in primary sensory neurons 31 and increases pro-dynorphin mRNA in dorsal horn neurons.…”

Zolpidem increases bladder capacity and decreases urine excretion in rats

“…Blok et al 18 demonstrated a direct pathway from the pontine micturition center to the dorsal gray commissure of the sacral cord in cats, 18 and suggested that the pathway relaxed the external striated sphincter during micturition via inhibitory modulation through GABA neurons in Onuf's nucleus. Furthermore, Kanie et al, 16 who performed many experiments on the mechanisms underlying bladder overactivity in CI rats, suggested that the impairment of the inhibitory GABAergic pathway that originates in the forebrain Neurourology and Urodynamics DOI 10.1002/nau Fig. 4.…”