, Volume 179, Issue 4, pp 733–741

Serotonergic neurons in the median raphe nucleus regulate inhibitory avoidance but not escape behavior in the rat elevated T-maze test of anxiety


  • Lucinéia dos Santos
    • Departament of Psychology and Education, FFCLRPUniversity of São Paulo
  • Telma G. C. S. de Andrade
    • Departament of Biological Science, FCLAUNESP
    • Departament of Pharmacology, School of MedicineUniversity of São Paulo
Original Investigation

DOI: 10.1007/s00213-004-2120-3

Cite this article as:
dos Santos, L., de Andrade, T.G.C.S. & Zangrossi, H. Psychopharmacology (2005) 179: 733. doi:10.1007/s00213-004-2120-3



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.


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.


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.


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-HT1A 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.


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.


Median raphe nucleusElevated T-mazeSerotoninGeneralized anxiety and panic

Copyright information

© Springer-Verlag 2004