Fear-reducing effects of intra-amygdala neuropeptide Y infusion in animal models of conditioned fear: an NPY Y1 receptor independent effect.
BACKGROUND
Neuropeptide Y (NPY) and its receptors are densely localized in brain regions involved in the mediation and modulation of fear, including the amygdala. Several studies showed that central NPY is involved in the modulation of fear and anxiety.


OBJECTIVE
In the present study, we investigated (1) whether intra-amygdala injections of NPY affect the expression of conditioned fear and (2) whether NPY Y1 receptors (Y1R) mediates the effects of these intra-amygdaloid NPY injections.


RESULTS
Intra-amygdala NPY injections robustly decreased the expression of conditioned fear measured by conditioned freezing and fear-potentiated startle. These NPY effects were not mimicked by intra-amygdala injections of the Y1R agonists Y-28 or Y-36, and co-infusion of the Y1R antagonist BIBO 3304 did not block the NPY effects. Furthermore, we tested Y1R-deficient mice in conditioned freezing and found no differences between wild type and mutant littermates. Finally, we injected NPY into the amygdala of Y1R-deficient mice. Y1R deficiency had no effect on the fear-reducing effects of intra-amygdala NPY.


CONCLUSIONS
These data show an important role of the transmitter NPY within the amygdala for the expression of conditioned fear. Y1R do not appear to be involved in the mediation of the observed intra-amygdala NPY effects suggesting that these effects are mediated via other NPY receptors.
Fendt
Markus
M
Novartis Institutes for BioMedical Research, Neuroscience DA, Neuropsychiatry, Forum 1, Novartis Campus, WSJ-386.3.28, 4056, Basel, Switzerland. markus.fendt@novartis.com
Bürki
Hugo
H
Imobersteg
Stefan
S
Lingenhöhl
Kurt
K
McAllister
Kevin H
KH
Orain
David
D
Uzunov
Doncho P
DP
Chaperon
Frederique
F
D000679:Amygdala / Q000187:drug effects*; D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003214:Conditioning, Classical / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004597:Electroshock / Q000009:adverse effects; D005239:Fear / Q000187:drug effects*; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D023421:Models, Animal; D009478:Neuropeptide Y / Q000172:deficiency / Q000494:pharmacology*; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D017476:Receptors, Neuropeptide Y / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013997:Time Factors
D009478:Neuropeptide Y; D020319:Oligodeoxyribonucleotides, Antisense; D010446:Peptide Fragments; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; D001120:Arginine; C117416:BIBO 3304