PT  - JOURNAL ARTICLE
AU  - Zul Merali
AU  - Tania Bédard
AU  - Nick Andrews
AU  - Ben Davis
AU  - Alexander T. McKnight
AU  - M. Isabel Gonzalez
AU  - Martyn Pritchard
AU  - Pam Kent
AU  - Hymie Anisman
TI  - Bombesin Receptors as a Novel Anti-Anxiety Therapeutic Target: BB<sub>1</sub> Receptor Actions on Anxiety through Alterations of Serotonin Activity
AID  - 10.1523/JNEUROSCI.1219-06.2006
DP  - 2006 Oct 11
TA  - The Journal of Neuroscience
PG  - 10387--10396
VI  - 26
IP  - 41
4099  - http://www.jneurosci.org/content/26/41/10387.short
4100  - http://www.jneurosci.org/content/26/41/10387.full
SO  - J. Neurosci.2006 Oct 11; 26
AB  - The effects of PD 176252 [3-(1H-indol-3-yl)-N-[1-(5-methoxy-pyridin-2-yl)-cyclohexylmethyl]-2-methyl-2-[3-(nitro-phenyl)ureido]propionamide], a nonpeptide bombesin (BB) BB1/BB2 receptor antagonist, were assessed in rats using several ethologically relevant tests of anxiety. Consistent with a role for the bombesin family of peptides in subserving anxiety behaviors, the antagonist increased social interaction (3.75 and 7.5 mg/kg, i.p.), dose-dependently attenuated the number of vocalizations emitted by guinea pig pups separated from their mother (1–30 mg/kg, i.p.), reduced latency to approach a palatable snack in an anxiogenic (unfamiliar) environment, and reduced the fear-potentiated startle response (5 and 10 mg/kg, i.p., and 100–200 ng per rat, i.c.v.). When administered directly to the dorsal raphé nucleus (DRN), PD 176252 (20–500 ng) increased social interaction under aversive conditions, as did the 5-HT1A receptor agonist 8-hydroxy-2(di-n-propylamino)tetralin (50 ng). Furthermore, intra-DRN microinfusion of the peptide antagonist (PD 176252) suppressed, whereas its agonist [neuromedin B (NMB)-30] promoted, the in vivo release of 5-HT in the ventral hippocampus. In parallel, the suppressed social interaction elicited by intra-DRN administration of NMB was attenuated by a systemically administered 5-HT2C (but not 5-HT1A) receptor antagonist. Together, these findings suggest that endogenous BB-like peptides at the DRN evoke the release of 5-HT from the limbic nerve terminals originating from the raphé, specifically at the ventral hippocampus, resulting in anxiogenesis. The finding that this action was attenuated by BB receptor (BB1 and/or BB2) antagonists suggests that these compounds may represent a novel class of anxiolytic agents.