5-HT1A and 5-HT2A receptors in the rat dorsal periaqueductal gray mediate the antipanic-like effect induced by the stimulation of serotonergic neurons in the dorsal raphe nucleus

Psychopharmacology (2005) 183: 314321

DOI 10.1007/s00213-005-0196-zORIGINAL INVESTIGATIONRoger L. H. Pobbe . Hlio Zangrossi Jr5-HT1A and 5-HT2A receptors in the rat dorsal periaqueductal gray

mediate the antipanic-like effect induced by the stimulationof serotonergic neurons in the dorsal raphe nucleusReceived: 6 April 2005 / Accepted: 6 September 2005 / Published online: 18 October 2005

# Springer-Verlag 2005Abstract Rationale: It has been proposed that the

serotonergic pathway that connects the dorsal raphe nucleus

(DRN) to the dorsal periaqueductal gray (DPAG) is

implicated in the regulation of escape, a behavior that has

been related to panic. Objectives: We further evaluated

this hypothesis by investigating whether intra-DRN injection of the 5-HT1A receptor antagonist WAY-100635

changes the escape response of rats submitted to the

elevated T-maze. This test also measures inhibitory avoidance, which has been associated with generalized anxiety

disorder. We also investigated whether the 5-HT1A and 5-

HT2A receptors in the DPAG mediate the behavioral

consequences induced by the injection of WAY-100635

into the DRN. Results: Intra-DRN injection of WAY-

100635 facilitated inhibitory avoidance, while impairing

escape. The same effect was obtained after intra-DRN

injection of the glutamate receptor agonist kainic acid.

Preadministration of WAY-100635 into the DPAG counteracted the effect induced by intra-DRN injection of

WAY-100635 and of kainic acid on escape, but not on

inhibitory avoidance. Preadministration of the preferential

5-HT2A receptor antagonist ketanserin into the DPAG

abolished the effects of intra-DRN injection of WAY-

100635 on both elevated T-maze tasks. Conclusion: The

results are indicative that 5-HT1A autoreceptors in the

DRN are under tonic inhibitory influence by endogenous

5-HT. The effects of 5-HT release in the DPAG after intra-

DRN injection of WAY-100635 and kainic acid on inhibitory avoidance and escape involve different 5-HT receptor

subtypes. Whereas 5-HT2A receptors in the DPAG seem to

mediate the effect of 5-HT on both behaviors, 5-HT1A

receptors are only involved in the regulation of escape.Keywords Serotonin . WAY-100635 . Ketanserin .

Generalized anxiety . Panic . Elevated T-mazeIntroductionSerotonergic neurons of the dorsal raphe nucleus (DRN)

have been implicated in the physiopathology of anxiety

(Chaouloff 2000; Abrams et al. 2004). Based on a wealth of

clinical and experimental evidence, Deakin and Graeff

(1991) have proposed that two serotonergic pathways

originated in this nucleus, by innervating brain substrates

controlling distinctive defensive behaviors,...