Interactions between glutamatergic and monoaminergic systems controlling the micturition reflex in the urethane-anesthetized rat.
The effects of MK-801 (0.001-3 mg/kg i.v.), a non-competitive NMDA glutamate receptor antagonist, on the micturition reflex were examined during continuous saline infusion (0.21 ml/min) cystometrograms (CMGs) in urethane-anesthetized (1.2 g/kg s.c.) rats pretreated with either reserpine (5 mg/kg i.p.), p-chlorophenylalanine (p-CPA; 150 mg/kg i.p., twice a day, 3 consecutive days), L-DOPA (200 mg/kg i.p. + carbidopa 100 mg/kg i.p.) or apomorphine (10 mg/kg i.v.). Pretreatment with reserpine 8-12 h prior to the CMG recording, antagonized the inhibitory effect of MK-801 on the amplitude of micturition contractions while pretreatment with vehicle had no effect. However, pretreatment with the same dose of reserpine 18-22 h prior to the experiment failed to antagonize the inhibitory effect of MK-801. Both reserpine pretreatments enhanced the amplitude of reflex bladder contractions. Pretreatment with p-CPA did not alter bladder activity or the inhibitory effect of MK-801 on amplitude of micturition contractions. When administered 15 min prior to the MK-801, L-DOPA or apomorphine reduced by 70% or 63%, respectively, the maximal inhibitory effect of MK-801 on the amplitude of reflex bladder contractions. These data suggest that there is an interaction between glutamatergic and monoaminergic mechanisms in the regulation of micturition reflex. Since reserpine which reduces both catecholamine and serotonin levels in the nervous system altered the depressant effect of MK-801 on bladder activity, but p-CPA, an agent which depletes serotonin stores, did not, it is concluded that catecholaminergic pathways are involved in this interaction.(ABSTRACT TRUNCATED AT 250 WORDS)
Yoshiyama
M
M
Department of Pharmacology, School of Medicine, University of Pittsburgh, PA 15261.
Roppolo
J R
JR
de Groat
W C
WC
D000758:Anesthesia; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D015306:Biogenic Monoamines / Q000502:physiology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005260:Female; D010134:Fenclonine / Q000494:pharmacology; D005971:Glutamates / Q000502:physiology*; D018698:Glutamic Acid; D007980:Levodopa / Q000494:pharmacology; D010525:Peripheral Nerves / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects*; D012110:Reserpine / Q000494:pharmacology; D014520:Urethane; D014554:Urination / Q000502:physiology*
D015306:Biogenic Monoamines; D005971:Glutamates; D014520:Urethane; D018698:Glutamic Acid; D007980:Levodopa; D016291:Dizocilpine Maleate; D012110:Reserpine; D001058:Apomorphine; D010134:Fenclonine