title: Role of nitric oxide in the stress-induced release of serotonin in the locus coeruleus.
abstract: Serotonergic mechanisms within the locus coeruleus (LC) are thought to be important in various functions including the stress response. In this study we investigated a possible role of nitric oxide (NO) as an intermediary messenger in the regulation of the serotonin (5-HT) neurotransmission within the LC. Using the push-pull superfusion technique coupled with HPLC and electrochemical detection, the in vivo release of 5-HT was determined in time periods of 10 min in the LC of freely moving rats. Superfusion with three different NO donors, SIN-1 (linsidomine), S-nitroso-N-penicillamine (SNAP) or 3-(2-hydroxy-2-nitroso-1-propylhydrazino)-1-propanamine (PAPANO) increased 5-HT release in the LC. Superfusion with the precursor of NO, L-arginine, for 1 h led to a sustained increase in 5-HT release. On the other hand, the NOS inhibitor N-methyl-L-arginine methyl ester (L-NAME) did not significantly change the release of 5-HT. Infusion of N-methyl-D-aspartate (NMDA) or kainic acid, as well as exposure of rats to noise stress or tail pinch increased the release of 5-HT in the LC. Superfusion with L-NAME prevented the increase in 5-HT outflow by all these procedures, while the inactive isomer D-NAME had no effect. Taken together, the results of this study suggest that the release of 5-HT in the LC is facilitated by NO. Under resting conditions inhibition of NOS does not appear to substantially influence the release of 5-HT in the LC. However, there seems to be a facilitatory nitrergic influence on serotonergic responses evoked by excitatory amino acid receptor stimulation or various stress stimuli.
authors.affiliation: Department of Pharmacology and Toxicology, University of Innsbruck, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Sinner
authors.forename: S T
authors.initials: ST
authors.lastname: Kaehler
authors.forename: A
authors.initials: A
authors.lastname: Philippu
authors.forename: N
authors.initials: N
authors.lastname: Singewald
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008125:Locus Coeruleus / Q000378:metabolism*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D013312:Stress, Physiological / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D012701:Serotonin; D019331:NG-Nitroarginine Methyl Ester