Effect of 5-HT1A receptor-mediated serotonin augmentation on Fos immunoreactivity in rat brain.
The consequences of pharmacologically evoked augmented serotonin (5-hydroxytryptamine, 5-HT) release on neuronal activity in the brain, as reflected by the cellular expression of the immediate early gene c-fos, were studied. Wistar rats were treated with saline, the 5-HT reuptake inhibitor citalopram (10 micromol/kg s.c.), the 5-HT(1A) receptor antagonist N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)-N-(2-pyridyl)cyclohexane carboxamine trihydrochloride (WAY 100635, 1 micromol/kg s.c.), or the combination of both drugs. At the given dosages, the combination of the drugs has previously been shown to enhance the cerebral release of 5-HT. Two hours and thirty minutes after administration, the brains were fixated, and Fos protein was histologically stained and quantified. The paraventricular nucleus of the hypothalamus, the central nucleus amygdala, the ventromedial hypothalamic nucleus, the dorsolateral striatum, and the nucleus accumbens shell were particularly responsive to increased 5-HT release. The results, illustrating the synergistic consequence of the combined drug treatments, are discussed in terms of activity of the limbic-hypothalamic-pituitary-adrenocortical system.
Jongsma
Minke E
ME
Department of Biological Psychiatry, University Hospital Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. M.E.Jongsma@acggn.azg.nl
Sebens
Jantiena B
JB
Bosker
Fokko J
FJ
Korf
Jakob
J
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D015283:Citalopram / Q000494:pharmacology; D004357:Drug Synergism; D007150:Immunohistochemistry; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
D015283:Citalopram; D010879:Piperazines; D016760:Proto-Oncogene Proteins c-fos; D011725:Pyridines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide