The effects of synthetic and endogenous imidazoline binding site ligands on neuronal activity in discrete brain regions of naive and restraint-stressed rats.
We have mapped Fos expression to investigate brain regions activated by synthetic selective I(2) (BU224) and endogenous (harmane) imidazoline binding site ligands in naive and restraint-stressed rats. Systemic administration of BU224 or harmane to naive rats increased Fos-like immunoreactivity (FLI) in the hypothalamic paraventricular nucleus (PVN), hippocampal dentate gyrus (DG), central and medial nuclei of the amygdala (CeA, MeA) and the locus coeruleus (LC). FLI in restraint-stressed rats was increased in all 5 regions by harmane, and in the CeA, MeA and LC by BU224. Dual-labelling of FLI cells in the PVN of naive rats showed an increase in the number of corticotrophin-releasing-factor-containing cells (CRF) activated by BU224 and harmane. Several CRF-containing neurons in the PVN expressed alpha(1)-adrenoceptors and were densely surrounded by catecholaminergic axons and terminals. Our results provide a functional neuroanatomical framework which may explain the stimulatory effects of imidazoline ligands on basal and stress-induced neuronal and neuroendocrine activity.
Smith
Karen L
KL
Department of Pharmacology and Therapeutics, National University of Ireland-Galway, University Road, Galway, Ireland.
Roche
Michelle
M
Jessop
David S
DS
Finn
David P
DP
D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D006247:Harmine / Q000031:analogs & derivatives / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D048288:Imidazolines / Q000378:metabolism* / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009498:Neurotoxins / Q000494:pharmacology; D016761:Oncogene Proteins v-fos / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical / Q000379:methods; D013315:Stress, Psychological / Q000473:pathology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
C105826:BU 224; D007093:Imidazoles; D048288:Imidazolines; D009498:Neurotoxins; D016761:Oncogene Proteins v-fos; D006247:Harmine; C005010:harman; D003346:Corticotropin-Releasing Hormone; D014446:Tyrosine 3-Monooxygenase