Gastrin-releasing peptide mediated regulation of 5-HT neuronal activity in the hypothalamic paraventricular nucleus under basal and restraint stress conditions.
The purpose of this study was to examine the gastrin-releasing peptide (GRP) mediated regulation of 5-HT neuronal activity in the paraventricular nucleus of the hypothalamus under basal and restraint stress conditions. Intracerebroventricular (icv) administration of GRP (1, 10, 100 ng/rat) increased 5-HIAA concentrations in the paraventricular nucleus (PVN) of the hypothalamus, but was without effect in the accumbens, suprachiasmatic and arcuate nuclei. Administration of (Leu(13)-psi-CH(2)NH-Leu(14)) Bombesin (10, 100 and 1000 ng/rat; icv), a GRP antagonist, had no effect by itself on PVN serotonergic activity; however, a dose of 1 microg/rat of this compound, completely blocked the increase of 5-HIAA concentrations induced by GRP (10 ng). Restraint stress increased serotonergic activity -as shown by an elevation of 5-HIAA in the PVN- as well as plasma ACTH and corticosterone. This stress-induced activation of both the serotonergic neurons and the hypothalamus-pituitary-adrenal axis was blocked by CRF and GRP antagonists. Interestingly, when the activation of hypothalamic 5-HT neurons was induced by GRP administration, alpha-helical (9-41) CRF was ineffective. These data suggest that GRP, by acting on GRP receptors but not via CRF receptors, increases 5-HT neuronal activity in the PVN. In turn, it appears that endogenous GRP and CRF receptor ligands are both simultaneously involved in the regulation of the increase in 5-HT neuronal activity, ACTH and corticosterone secretion, under stress conditions.
Departamento de Farmacología, Facultad de Farmacia, and Unidad de Cartografía Cerebral, Instituto Pluridisciplinar, Universidad Complutense de Madrid, 28040, Madrid, Spain.
Margarita M
MM
Garrido
José A
JA
Fuentes
Jorge
J
Manzanares
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001839:Bombesin / Q000031:analogs & derivatives* / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D019886:Gastrin-Releasing Peptide / Q000494:pharmacology* / Q000502:physiology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D012701:Serotonin / Q000378:metabolism*
D010446:Peptide Fragments; C057644:bombesin, Leu(13)-psi-CH2NH-Leu(14)-; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D019886:Gastrin-Releasing Peptide; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; C045089:corticotropin releasing hormone (9-41); D001839:Bombesin; D003345:Corticosterone