Serotonergic neurons in the median raphe nucleus regulate inhibitory avoidance but not escape behavior in the rat elevated T-maze test of anxiety.
BACKGROUND
A wealth of evidence supports the involvement of the serotonergic neurons of the median raphe nucleus (MRN) in anxiety. However, it is presently unclear whether serotonergic pathways arising from this nucleus play distinguishing regulatory roles in defensive behaviors that have been associated with specific subtypes of anxiety disorders.


OBJECTIVE
To evaluate the role of the MRN serotonergic neurons in the regulation of two defensive behaviors, inhibitory avoidance and escape, which have been related, respectively, to generalized anxiety and panic disorders.


METHODS
Male Wistar rats were submitted to the elevated T-maze test of anxiety after intra-MRN administration of drugs that either non-selectively or selectively change the activity of the serotonergic neurons.


RESULTS
Intra-MRN injection of FG 7142 (0.04 and 0.08 nmol) and kainic acid (0.03 and 0.06 nmol), drugs that non-selectively stimulate the MRN serotonergic neurons, facilitated inhibitory avoidance acquisition, but impaired escape performance. Microinjection of muscimol (0.11 and 0.22 nmol), a compound that non-selectively inhibits the activity of the MRN serotonergic neurons, impaired inhibitory avoidance and facilitated escape performance. Both kainic acid and muscimol also changed rat locomotion in the open-field test. Intra-MRN injection of 8-OH-DPAT (0.6-15 nmol) and WAY-100635 (0.18-0.74 nmol), respectively an agonist and an antagonist of somatodendritic 5-HT(1A) receptors located on serotonergic neurons of the MRN, only affected inhibitory avoidance-while the former inhibited the acquisition of this behavior, the latter facilitated it.


CONCLUSIONS
MRN serotonergic neurons seem to be selectively involved in the regulation of inhibitory avoidance in the elevated T-maze. This result supports the proposal that 5-HT pathways departing from this nucleus play an important role in anxiety processing, with implications for pathologies such as generalized anxiety disorder.
Dos Santos
Lucinéia
L
Departament of Psychology and Education, FFCLRP, University of São Paulo, 14040-901, Ribeirão Preto, SP, Brazil.
de Andrade
Telma G C S
TG
Zangrossi
Hélio
H
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001007:Anxiety / Q000523:psychology*; D001362:Avoidance Learning / Q000502:physiology*; D002243:Carbolines / Q000494:pharmacology; D004924:Escape Reaction / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009118:Muscimol / Q000494:pharmacology; D009474:Neurons / 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 / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D002243:Carbolines; D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C104425:serotonin 7 receptor; D044282:Receptor, Serotonin, 5-HT1A; D009118:Muscimol; D012701:Serotonin; C035874:FG 7142; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007608:Kainic Acid