[Abstract Title]. - Society for Neuroscience

stressed vs. unstressed rats. In particular, in unstressed rats CRF1 is more abundant on the plasma
membrane while CRF2 is largely restricted to the cytoplasm. Following a single exposure to
swim stress (24 h later), CRF2 is recruited to the plasma membrane and although CRF1 tended to
be internalized, this change was not significant. The present studies examined the consequences
of stress-related receptor trafficking and whether CRF1 activation was necessary for this effect.
CRF (30 ng, intra-raphe) decreased DRN neuronal activity of unstressed rats, as previously
reported. In contrast, this same dose activated DRN neurons when administered 24 h after swim
stress. The CRF-elicited excitation of DRN neurons was abrogated when stressed rats were
pretreated with the selective CRF2 antagonist antisauvagine-30. Indeed, CRF administered in
previously stressed rats that were pretreated with antisauvagine-30 inhibited DRN activity by a
similar magnitude as was seen in unstressed rats. Finally, ultrastructural analysis revealed that
administration of the selective CRF1 antagonist antalarmin prior to swim stress prevented CRF2
recruitment to the plasma membrane 24 hours later. Taken with our previous studies, these data
support a model whereby stress induces the recruitment of CRF2 from the cytoplasm to the
plasma membrate in DRN neurons resulting in a qualitative shift of the CRF response from
inhibition to excitation. Further, the unmasking of CRF-induced inhibition by antisauvagine-30
in stressed rats is consistent with the continued presence of CRF1 at the plasma membrane
sufficient to mediate an inhibitory response. Finally, the attenuation of CRF2 redistribution to the
plasma membrane following blockade of CRF1 suggests the initial CRF1 activation is necessary
for CRF2 trafficking. In summary, these findings suggest that actions at CRF1 or CRF2
predominate in the DRN of unstressed and stressed rats, respectively, and that CRF2 availability
may depend on the accessibility of CRF1 in the DRN when there is a history of prior stress.
Disclosures: M. Waselus , None; C. Nazzaro, None; R.J. Valentino, None; B.S. Reyes,
None; E.J. Van Bockstaele, None.
Poster
284. Regulation of Food Intake and Body Weight: Integration of Peripheral Signals:
Systems
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 284.1/PP24
Topic: E.07.b. Integration of peripheral signals: Systems
Support: NIH AG 027697
Biomedical Health Research Initiative, MSU
Title: Chronic metformin treatment reverses the obese phenotype in diet-induced obese (DIO)
rats placed on a high-fat (HF) diet