title: Corticotropin-releasing factor binding protein within the ventral tegmental area is expressed in a subset of dopaminergic neurons.
abstract: Corticotropin-releasing factor (CRF) and related peptides play a role in mediating neuronal effects of stress. These peptides mediate stress responses by their interactions with the CRF receptors and the CRF-binding protein (CRF-BP). Because the CRF-BP is implicated in neurotransmission within the ventral tegmental area (VTA), we investigated whether the CRF-BP is expressed in VTA neurons. By in situ hybridization, we detected cellular expression of CRF-BP mRNA in the VTA; no such expression was seen in neighboring substantia nigra pars compacta (SNC) or substantia nigra pars reticulata. By double in situ hybridization, we determined that VTA neurons with CRF-BP mRNA coexpressed transcripts encoding either tyrosine hydroxylase [TH; a marker for dopamine (DA) neurons] or glutamic acid decarboxylase [GAD; synthesizing enzyme of gamma-aminobutyric acid (GABA)]. Neurons with CRF-BP mRNA represented 25% of the total population of TH-expressing neurons and 28% of the total population of GAD-expressing neurons, indicating that discrete subpopulations of dopaminergic and GABAergic neurons are present in the VTA. Within the total population of neurons containing CRF-BP mRNA, 70% coexpressed TH mRNA and only 27% coexpressed GAD mRNA. As far as we are aware, we provide the first anatomical evidence that a molecule, CRF-BP, is encoded by DAergic neurons of the VTA but not by those of the SNC. We propose, based on the observation that the majority of VTA neurons expressing CRF-BP mRNA are DAergic, that in the VTA interactions of CRF-BP with CRF, or with CRF-related peptides, are likely to be mediated predominantly by DAergic neurons.
authors.affiliation: Intramural Research Program, Cellular Neurophysiology, National Institute on Drug Abuse, Biomedical Research Center, Baltimore, Maryland 21224, USA.
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Wang
authors.forename: Marisela
authors.initials: M
authors.lastname: Morales
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis*; D004298:Dopamine / Q000378:metabolism; D015870:Gene Expression; D005968:Glutamate Decarboxylase / Q000096:biosynthesis; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D009474:Neurons / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis; D017557:Ventral Tegmental Area / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D012333:RNA, Messenger; C067133:corticotropin releasing factor-binding protein; D014446:Tyrosine 3-Monooxygenase; D005968:Glutamate Decarboxylase; D004298:Dopamine