Glutamatergic and dopaminergic contributions to rat bladder hyperactivity after cerebral artery occlusion.
The contribution of glutamatergic and dopaminergic mechanisms to bladder hyperactivity after left middle cerebral artery occlusion was evaluated by determining the effects of intravenous cumulative doses of an N-methyl-D-aspartate (NMDA) glutamatergic antagonist (MK-801) and D1-selective (Sch-23390), D2-selective (sulpiride), or nonselective (haloperidol) dopaminergic antagonists on bladder activity in sham-operated (SO) and cerebral-infarcted (CI) rats. MK-801 (1 and 10 mg/kg) or sulpiride (3-30 mg/kg) significantly increased bladder capacity (BC) in CI but decreased or had no effect, respectively, on BC in SO. Sch-23390 (0.1-3 mg/kg) decreased BC in both SO and CI. In both CI and SO, low doses of haloperidol (0.1-1 mg/kg) increased BC, but a higher dose (3 mg/kg) reversed this effect. Administration of haloperidol (0.3 mg/kg) or sulpiride (10 mg/kg) in combination with MK-801 (0.01-10 mg/kg) markedly increased BC in CI but produced small decreases or increases in BC depending on the dose of MK-801 in SO. These results indicate that the bladder hyperactivity induced by cerebral infarction is mediated in part by NMDA glutamatergic and D2 dopaminergic excitatory mechanisms.
Yokoyama
O
O
Department of Pharmacology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA. oyoko@med.kanazawa-u.ac.jp
Yoshiyama
M
M
Namiki
M
M
de Groat
W C
WC
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000503:physiopathology*; D001552:Benzazepines / Q000494:pharmacology; D002544:Cerebral Infarction / Q000503:physiopathology; D002561:Cerebrovascular Disorders / Q000503:physiopathology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D018698:Glutamic Acid / Q000502:physiology*; D006220:Haloperidol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013469:Sulpiride / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects / Q000503:physiopathology*; D001750:Urinary Bladder, Neurogenic / Q000503:physiopathology*
D001552:Benzazepines; D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D013469:Sulpiride; D006220:Haloperidol; D004298:Dopamine