A role for midbrain raphe gamma aminobutyric acid neurons in 5-hydroxytryptamine feedback control.
New data show that 5-hydroxytryptamine (5-HT) neurons of the dorsal raphe nucleus (DRN) are subject to feedback control from 5-HT2 receptors, but the circuitry involved is uncertain. This study investigated whether 5-HT2 receptor agonism activates DRN gamma-aminobutyric acid (GABA) neurons, which are known to inhibit neighbouring 5-HT neurons. Systemic administration of the 5-HT2 receptor agonist, DOI, caused a striking increase in Fos-immunoreactivity in the DRN. This effect was abolished by the 5-HT2 antagonists ritanserin and MDL 100907, but not SB 206553, indicating the involvement of 5-HT2A receptors. Importantly, DOI-induced Fos-immunoreactivity in the DRN was extensively colocalized in GAD67-immunoreactive neurons. These findings suggest that activated local GABA neurons may play an important role in 5-HT2 receptor-mediated feedback control of DRN 5-HT neurons.
Boothman
Laura J
LJ
University Department of Pharmacology, Mansfield Road, Oxford, OX1 3QT, UK.
Sharp
Trevor
T
D000662:Amphetamines / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D002452:Cell Count; D005246:Feedback / Q000502:physiology*; D005464:Fluorobenzenes / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005968:Glutamate Decarboxylase / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D016761:Oncogene Proteins v-fos / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000662:Amphetamines; D005464:Fluorobenzenes; D007527:Isoenzymes; D016761:Oncogene Proteins v-fos; D010880:Piperidines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C079049:volinanserin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine