title: Changes in dopaminergic and glutamatergic excitatory mechanisms of micturition reflex after middle cerebral artery occlusion in conscious rats.
abstract: Previous reports have shown that N-methyl-d-aspartate (NMDA) glutamatergic and D2 dopaminergic mechanisms have independent excitatory effects on bladder activity in normal and cerebral infarcted (CI) rats under urethane anesthesia. The study presented here was undertaken to investigate the interaction between these two mechanisms on bladder activity in conscious Sprague-Dawley female rats with or without cerebral infarction. Occlusion of the left middle cerebral artery or a sham operation (SO) was performed under halothane anesthesia. After recovery from the anesthesia, bladder activity was monitored continuously by means of infusion cystometrography in awake rats. The effects of cumulative intravenous doses of quinpirole (0.001-1 mg/kg), a D2 dopamine receptor agonist, were studied in awake SO and CI rats with or without dizocilpine (10 mg/kg) pretreatment. The effects of dizocilpine (1 or 10 mg/kg) were also examined in other SO or CI rats pretreated with 1 mg/kg of quinpirole. Bladder capacity in CI rats was significantly smaller (0.18 ml) than that in SO rats (0.48 ml). Quinpirole (0.1 and 1 mg/kg) further reduced bladder capacity in both types of rats, an effect blocked by sulpiride (20 mg/kg), a D2 dopamine receptor antagonist. The effect of quinpirole was also antagonized by dizocilpine (1 mg/kg) to a significantly (P < 0.01) greater degree in CI than in SO rats. In SO rats pretreated with 1 mg/kg of quinpirole, dizocilpine significantly increased bladder capacity in a dose-dependent manner. After the maximum dose (10 mg/kg) of dizocilpine, sulpiride did not produce any changes in bladder activity. In CI rats pretreated with 1 mg/kg of quinpirole, 1 mg/kg of dizocilpine increased bladder capacity. After administration of the maximum dose of dizocilpine (10 mg/kg), which did not produce an additional effect, sulpiride (20 mg/kg) increased bladder capacity by 58.3%. These results indicate that in awake rats D2 dopaminergic excitatory effects on the urinary bladder are mediated in part by NMDA glutamatergic mechanisms and in part by non-NMDA mechanisms. The latter type was more prominent in CI rats, indicating that the bladder hyperactivity induced by cerebral infarction may be mediated by an alteration in dopaminergic-glutamatergic interactions in the brain.
authors.affiliation: Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: Osamu
authors.initials: O
authors.lastname: Yokoyama
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Yoshiyama
authors.forename: Mikio
authors.initials: M
authors.lastname: Namiki
authors.forename: William C
authors.initials: WC
authors.lastname: de Groat
mesh_terms: D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D013469:Sulpiride / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects / Q000503:physiopathology; D001750:Urinary Bladder, Neurogenic / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D014554:Urination / Q000187:drug effects / Q000502:physiology; D014851:Wakefulness
chemical_list: D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D019257:Quinpirole; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D013469:Sulpiride; D004298:Dopamine