[Effect of nitric oxide on central dopaminergic neurons].
Neuronal damage induced by ischemia involves various changes in neurotransmission. Nitric oxide (NO), a putative neurotransmitter and/or neuromodulator has some role in this neuronal damage. In the present study, the effect of NO on the terminal site of dopamine (DA) neurons in the rat striatum was examined using the microdialysis technique. First perfusion with sodium nitroprusside (SNP) as an NO donor increased extracellular DA (10 mM, 460%; 1 mM, 140%) in the striatum and decreased its metabolites. Pretreatment with tetrodotoxin (TTX, 5 microM), (+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine hydrogen maleato (MK801, 1 microM) or muscimol (1 microM) inhibited SNP-induced increases in extracellular DA and decreases in DOPAC (TTX, complete block; MK801, 75% inhibition; muscimol, 80% inhibition). Second, extracellular NO, DA and DOPAC were measured in the gerbil striatum following 10 minutes of forebrain ischemia produced by occluding both carotid arteries. Occlusion of the carotid arteries also caused increases in extracellular NO and DA in the gerbil striatum (NO, 3000%; DA, 2800%). These findings suggest that NO-facilitated DA release occurs via interaction between glutamatergic and dopaminergic neurons. These changes are probably partially involved in the neurodegenerative phenomena following ischemia. It is also shown that simultaneous measurements of NO and DA using this technique may be useful in assessing ischemic changes in vivo.
Nakahara
K
K
Department of Pharmacology, Kurume University School of Medicine, Japan.
Yokoo
H
H
Yoshida
M
M
Tanaka
M
M
Shigemori
M
M
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D005849:Gerbillinae; D008297:Male; D017551:Microdialysis; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013779:Tetrodotoxin / Q000494:pharmacology
D015102:3,4-Dihydroxyphenylacetic Acid; D009599:Nitroprusside; D009569:Nitric Oxide; D013779:Tetrodotoxin; D016291:Dizocilpine Maleate; D004298:Dopamine