5-HT(1A) and 5-HT(2A) receptors in the rat dorsal periaqueductal gray mediate the antipanic-like effect induced by the stimulation of serotonergic neurons in the dorsal raphe nucleus.
BACKGROUND
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.


OBJECTIVE
We further evaluated this hypothesis by investigating whether intra-DRN injection of the 5-HT(1A) 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-HT(1A) and 5-HT(2A) 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-HT(2A) receptor antagonist ketanserin into the DPAG abolished the effects of intra-DRN injection of WAY-100635 on both elevated T-maze tasks.


CONCLUSIONS
The results are indicative that 5-HT(1A) 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-HT(2A) receptors in the DPAG seem to mediate the effect of 5-HT on both behaviors, 5-HT(1A) receptors are only involved in the regulation of escape.
Pobbe
Roger L H
RL
Department of Pharmacology, School of Medicine, University of São Paulo, Av. Bandeirantes 3900, 14049-900 Ribeirão Preto, Brazil.
Zangrossi
Hélio
H
D000818:Animals; D007608:Kainic Acid / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D016584:Panic Disorder / Q000517:prevention & control*; D010487:Periaqueductal Gray / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology*
D010879:Piperazines; D011725:Pyridines; D044402:Receptor, Serotonin, 5-HT2A; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D007650:Ketanserin; D007608:Kainic Acid