Eur J Neurosci. 2015 Oct 27. doi: 10.1111/ejn.13113.
There is significant functional evidence showing that corticotropin releasing factor type-2 receptor (CRF2 R) and corticotropin releasing factor-binding protein (CRF-BP) regulate glutamatergic synapses onto ventral tegmental area dopaminergic neurons. It has been shown that CRF requires CRF-BP to potentiate N-methyl-D-aspartate receptors in dopaminergic neurons through CRF2 R, and that increases glutamate release in cocaine-treated rats through the activation of CRF2 R only by agonists with high affinity to CRF-BP. Furthermore, this CRF-mediated increase in ventral tegmental area glutamate is responsible for stress-induced relapse to cocaine-seeking behavior.
However, there is lack of anatomical evidence to explain the mechanisms of CRF actions in ventral tegmental area.
Thus, we studied whether CRF2 R and CRF-BP are expressed in ventral tegmental area nerve terminals, using a synaptosomal preparation devoid of postsynaptic elements.
Our results show that both proteins are co-expressed in glutamatergic and GABAergic ventral tegmental area synaptosomes. A main glutamatergic input to the ventral tegmental area that has been associated to addictive behavior is originated in the lateral hypothalamic area. Thus, we focused our study in the lateral hypothalamic area-ventral tegmental area input using orexin as a marker of this input.
Our results show that CRF2 R and CRF-BP mRNA and protein are expressed in the lateral hypothalamic area and that both proteins are present in orexin-positive ventral tegmental area synaptosomes.
Our results showing that CRF2 R and CRF-BP are expressed in the lateral hypothalamic area-ventral tegmental area input give anatomical support to suggest that this input plays a role in stress-induced relapse to cocaine-seeking behavior.