title: The lateral habenula regulates defensive behaviors through changes in 5-HT-mediated neurotransmission in the dorsal periaqueductal gray matter.
abstract: Chemical stimulation of the lateral nucleus of the habenula (LHb), an area implicated in the regulation of serotonergic activity in raphe nuclei, affects the acquisition of inhibitory avoidance and escape expression of rats submitted to the elevated T-maze test of anxiety. Here, we investigated whether facilitation of 5-HT-mediated neurotransmission in the dorsal periaqueductal gray (dPAG) accounts for the behavioral consequences in the elevated T-maze induced by chemical stimulation of the LHb. The dPAG in the midbrain, which is innervated by 5-HT fibers originating from the dorsal raphe nucleus (DRN), has been consistently implicated in the genesis/regulation of anxiety- and fear-related defensive responses. The results showed that intra-dPAG injection of WAY-100635 or ketanserin, 5-HT(1A) and 5-HT(2A/2C) receptor antagonists, respectively, counteracted the anti-escape effect caused by bilateral intra-LHb injection of kainic acid (60pmol/0.2microl). Ketanserin, but not WAY-100635, blocked kainic acid's facilitatory effect on inhibitory avoidance acquisition. Overall, the results suggest that the pathway connecting the LHb to the DRN is involved in the control of 5-HT release in the dPAG, and facilitation of 5-HT-mediated neurotransmission in the latter area distinctively impacts upon the expression of anxiety- and fear-related defensive behaviors. While stimulation of 5-HT(1A) receptors selectively affects escape performance, 5-HT(2A/2C) receptors modulate both inhibitory avoidance and escape.
authors.affiliation: Department of Pharmacology, School of Medicine, University of São Paulo, Av. Bandeirantes, 3900, CEP 14049-900 Ribeirão Preto, Brazil. rogerlhp@usp.br
authors.forename: Roger Luis Henschel
authors.initials: RL
authors.lastname: Pobbe
authors.forename: Helio
authors.initials: H
authors.lastname: Zangrossi
mesh_terms: D000818:Animals; D001362:Avoidance Learning; D019262:Habenula / Q000502:physiology*; D007608:Kainic Acid / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010487:Periaqueductal Gray / Q000187:drug effects / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology; D044405:Receptor, Serotonin, 5-HT2C / Q000502:physiology; D012701:Serotonin / Q000502:physiology*; D058829:Serotonin 5-HT1 Receptor Antagonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D009435:Synaptic Transmission
chemical_list: D010879:Piperazines; D011725:Pyridines; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D058829:Serotonin 5-HT1 Receptor Antagonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D007650:Ketanserin; D007608:Kainic Acid