Corticotropin-releasing factor binding protein within the ventral tegmental area is expressed in a subset of dopaminergic neurons

J Comp Neurol. 2008 Jul 20;509(3):302-18. doi: 10.1002/cne.21751.


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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Carrier Proteins / biosynthesis*
  • Dopamine / metabolism
  • Gene Expression
  • Glutamate Decarboxylase / biosynthesis
  • Immunohistochemistry
  • In Situ Hybridization
  • Male
  • Neurons / metabolism*
  • RNA, Messenger / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Tyrosine 3-Monooxygenase / biosynthesis
  • Ventral Tegmental Area / metabolism*


  • Carrier Proteins
  • RNA, Messenger
  • corticotropin releasing factor-binding protein
  • Tyrosine 3-Monooxygenase
  • Glutamate Decarboxylase
  • Dopamine