PMID- 15953348 OWN - NLM STAT- MEDLINE DCOM- 20050808 LR - 20181201 IS - 0022-3042 (Print) IS - 0022-3042 (Linking) VI - 94 IP - 1 DP - 2005 Jul TI - Differential monoaminergic, neuroendocrine and behavioural responses after central administration of corticotropin-releasing factor receptor type 1 and type 2 agonists. PG - 45-56 AB - Corticotropin-releasing factor (CRF) mediates various aspects of the stress response. To differentiate between the roles of CRF(1) and CRF(2) receptor subtypes in monoaminergic neurotransmission, hypothalamic-pituitary-adrenocortical axis activity and behaviour we compared the effects of CRF and urocortin 1 with those of the selective CRF(2) receptor ligands urocortin 2 and urocortin 3. In vivo microdialysis in the rat hippocampus was used to assess free corticosterone, extracellular levels of serotonin (5-HT) and noradrenaline (NA), and their metabolites 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylglycol (MHPG), respectively. Intracerebroventricular (i.c.v.) injection of CRF and urocortin 1, 2 and 3 (1.0 microg) increased hippocampal levels of 5-HT and 5-HIAA. CRF and urocortin 1 increased NA and MHPG, whereas urocortin 2 and urocortin 3 elevated MHPG, but not NA levels. CRF and the urocortins induced an immediate increase in behavioural activity. CRF and urocortin 1 mainly caused grooming and exploratory behaviour. In contrast, urocortin 2 and urocortin 3 both induced exploratory behaviour, but not grooming, and increased time spent eating food pellets. All urocortins, but not CRF, suppressed food intake 4-6 h after injection. Hippocampal free corticosterone levels were elevated by CRF, urocortin 1 and 3, but not by urocortin 2. The time courses of the CRF- and urocortin 1-induced responses were significantly prolonged as compared to those of the CRF(2) receptor ligands. The stimulatory changes evoked by CRF and urocortin 1 were present up to 4-6 h after injection, whereas the effects of urocortin 2 and urocortin 3 returned to baseline within 2.5 h after injection. Pre-treatment with the selective antagonist antisauvagine-30 (5.0 microg, i.c.v.) confirmed that the effects of urocortin 3 were CRF(2) receptor-mediated. The differential time course of the monoaminergic, neuroendocrine and behavioural effects of CRF and urocortin 1, as compared to urocortin 2 and urocortin 3, and the specific behavioural pattern induced by the CRF(2) receptor ligands, suggest a distinct role for CRF(2) receptors in the stress response. FAU - de Groote, Lotte AU - de Groote L AD - Max Planck Institute of Psychiatry, Section of Neurochemistry, Munich, Germany. Lott.de-Groote@bristol.ac.uk FAU - Penalva, Rosana G AU - Penalva RG FAU - Flachskamm, Cornelia AU - Flachskamm C FAU - Reul, Johannes M H M AU - Reul JM FAU - Linthorst, Astrid C E AU - Linthorst AC LA - eng PT - Comparative Study PT - Journal Article PL - England TA - J Neurochem JT - Journal of neurochemistry JID - 2985190R RN - 0 (Biogenic Monoamines) RN - 0 (CRF receptor type 2) RN - 0 (Receptors, Corticotropin-Releasing Hormone) RN - 0 (Urocortins) RN - 0 (urocortin 2, mouse) RN - 5CLY6W2H1M (CRF receptor type 1) RN - 9015-71-8 (Corticotropin-Releasing Hormone) SB - IM EIN - J Neurochem. 2005 Aug;94(3):862-4 MH - Animals MH - Behavior, Animal/drug effects/*physiology MH - Biogenic Monoamines/*metabolism MH - Corticotropin-Releasing Hormone/administration & dosage MH - Humans MH - Injections, Intraventricular MH - Male MH - Mice MH - Neurosecretory Systems/drug effects/*metabolism MH - Rats MH - Rats, Wistar MH - Receptors, Corticotropin-Releasing Hormone/*agonists/metabolism MH - Urocortins EDAT- 2005/06/15 09:00 MHDA- 2005/08/09 09:00 CRDT- 2005/06/15 09:00 PHST- 2005/06/15 09:00 [pubmed] PHST- 2005/08/09 09:00 [medline] PHST- 2005/06/15 09:00 [entrez] AID - JNC3164 [pii] AID - 10.1111/j.1471-4159.2005.03164.x [doi] PST - ppublish SO - J Neurochem. 2005 Jul;94(1):45-56. doi: 10.1111/j.1471-4159.2005.03164.x.