Serotonin (5-HT) release in the dorsal raphé and ventral hippocampus: raphé control of somatodendritic and terminal 5-HT release.
Somatodendritic and terminal release of serotonin (5-HT) was investigated by simultaneously measuring extracellular concentrations of 5-HT, 5-hydroxyindole-3-acetic acid (5-HIAA) and homovanillic acid (HVA) in the dorsal raphé and ventral hippocampus in freely moving rats. Perfusion of tetrodotoxin (TTX, 1 microM and 10 microM) into the dorsal raphé simultaneously decreased dorsal raphé and hippocampal 5-HT release. However, following TTX perfusion into the hippocampus (10 microM), hippocampal 5-HT release was profoundly reduced but dorsal raphé 5-HT remained unchanged. Systemic injections with 5-HT1A agonist, buspirone (1.0-5.0 mg/kg, i.p.) decreased 5-HT and 5-HIAA and increased HVA concentrations in the dorsal raphé and in the hippocampus. The decreases in the raphé and hippocampal 5-HT induced by systemic buspirone were antagonized in rats pretreated with 1.0 mM (-) pindolol, locally perfused into the dorsal raphé. Local dorsal raphé perfusion of (-) pindolol alone (0.01-1.0 mM) increased dorsal raphé 5-HT and concomitantly induced a small increase in hippocampal 5-HT. Buspirone perfusion into the dorsal raphé did not change (10 nM, 100 nM), or produced a small increase (1.0 mM) in raphé 5-HT, without changing hippocampal 5-HT. These data provide evidence that 5-HT release in the dorsal raphé is dependent on the opening of fast activated sodium channels and that dorsal raphé 5-HT1A receptors control somatodendritic and hippocampal 5-HT release
Matos
F F
FF
Department of Neuropharmacology, Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT, USA.
Urban
C
C
Yocca
F D
FD
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002065:Buspirone / Q000494:pharmacology; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009411:Nerve Endings / Q000378:metabolism*; D010869:Pindolol / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D013779:Tetrodotoxin; D006897:Hydroxyindoleacetic Acid; D010869:Pindolol; D002065:Buspirone; D006719:Homovanillic Acid