Corticotropin-releasing factor type-2 receptor and corticotropin-releasing factor-binding protein coexist in rat ventral tegmental area nerve terminals originated in the lateral hypothalamic area.
There is significant functional evidence showing that corticotropin-releasing factor type-2 receptor (CRF2R) and corticotropin-releasing factor-binding protein (CRF-BP) regulate glutamatergic synapses onto ventral tegmental area (VTA) dopaminergic neurons. It has been shown that CRF requires CRF-BP to potentiate N-methyl-D-aspartate receptors in dopaminergic neurons through CRF2R, and that increases glutamate release in cocaine-treated rats through the activation of CRF2R only by agonists with high affinity to CRF-BP. Furthermore, this CRF-mediated increase in VTA glutamate is responsible for stress-induced relapse to cocaine-seeking behaviour. However, there is a lack of anatomical evidence to explain the mechanisms of CRF actions in VTA. Thus, it was studied whether CRF2R and CRF-BP are expressed in VTA nerve terminals, using a synaptosomal preparation devoid of postsynaptic elements. The current results show that both proteins are co-expressed in glutamatergic and γ-aminobutyric acid (GABA)ergic VTA synaptosomes. A main glutamatergic input to the VTA that has been associated to addictive behaviour is originated in the lateral hypothalamic area (LHA). Thus, this study was focused in the LHA-VTA input using orexin as a marker of this input. The results show that CRF2R and CRF-BP mRNA and protein are expressed in the LHA, and that both proteins are present in orexin-positive VTA synaptosomes. The results showing that CRF2R and CRF-BP are expressed in the LHA-VTA input give anatomical support to suggest that this input plays a role in stress-induced relapse to cocaine-seeking behaviour.
Department of Cellular and Molecular Biology, Millenium Science Nucleus in Stress and Addiction, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Alameda 340, Santiago, 8331150, Chile.
Paula G
PG
Slater
Department of Cellular and Molecular Biology, Millenium Science Nucleus in Stress and Addiction, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Alameda 340, Santiago, 8331150, Chile.
Veronica
V
Noches
Department of Cellular and Molecular Biology, Millenium Science Nucleus in Stress and Addiction, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Alameda 340, Santiago, 8331150, Chile.
Katia
K
Gysling
D000818:Animals; D001369:Axons / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D007026:Hypothalamic Area, Lateral / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000378:metabolism*; D000068797:Orexins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
C101531:CRF receptor type 2; D002352:Carrier Proteins; D000068797:Orexins; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; C067133:corticotropin releasing factor-binding protein; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid
VGLUT1; VGLUT2; orexin; synaptosomes; syntaxin 1