Nitric oxide-mediated regulation of dopamine release in the hippocampus in vivo.
Infusion of N-methyl-D-aspartate (NMDA) into the hippocampus of freely moving rats produced a concentration-dependent decrease in the extracellular levels of dopamine, an effect which was reversed by D-2-amino-5-phosphonovaleric acid (D-AP5). To determine the involvement of nitric oxide (NO) in this response, two nitric oxide synthase (NOS) inhibitors, N-nitro-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI), were examined for their ability to modify both basal and NMDA-inhibited dopamine release. When infused alone both NOS inhibitors elicited an increase in extracellular dopamine concentration, moreover, when administered prior to the application of NMDA, the agonist failed to elicit a decrease in dopamine levels. Infusion of the NO donor S-nitroso-N-acetylpenicillamine (SNAP) over a 30 min period caused either an increase or a decrease in dopamine release depending upon the concentration used. At the lower concentration (0.5 mM) SNAP promoted dopamine release whilst at the higher concentration (5 mM), the donor elicited a long lasting reduction in basal dopamine levels. The effect of the lower concentration of SNAP was reversed by the prior application of D-AP5, but that of the higher concentration was unaffected by the antagonist.
Segieth
J
J
Pharmacology Department, The School of Pharmacy, London, UK.
Fowler
L
L
Whitton
P
P
Pearce
B
B
D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism*; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D016202:N-Methylaspartate / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists
D018690:Excitatory Amino Acid Agonists; D007191:Indazoles; D020030:Nitric Oxide Donors; D016194:Receptors, N-Methyl-D-Aspartate; C110881:S-nitro-N-acetylpenicillamine; D009569:Nitric Oxide; D016202:N-Methylaspartate; D019001:Nitric Oxide Synthase; D010396:Penicillamine; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester; D004298:Dopamine