Aim: 

Learned helplessness (LH) and long-lasting pre-synaptic 5-HT and NA functions in the brain stem derived from exposure to acute immobilization stress was studied. The effect of the activation of the serotonergic receptor 5-HT_1A in these conditions was also evaluated.

Methods: 

Groups of animals with saline injection, injection of saline prior stress and injection of the 5-HT_1A receptor agonist 8-OH-DPAT prior stress were tested 24h later for passive avoidance and escape behaviour in an elevated T maze. Afterwards animals were perfused and a double immunolabelling of 5-HT and c-Fos immnunoreactivities (IR) was performed. The density of c-Fos/5-HT IR nerve cells and total 5-HT IR nerve cells were counted in midbrain raphe nuclei and c-Fos IR profiles in the locus coeruleus (LC).

Results: 

LH was developed 24h after the immobilization procedure. In the same group LH was associated with reduced density of 5-HT IR nerve cells in both DRN and MnRN probably related to a reduction of 5-HT synthesis. Neuronal activation as evaluated from expression of c-Fos IR in the dorsal raphe nucleus (DRN) and the LC was also inhibited in immobilized animals. Conversely, both LH appearance and the observed inhibitory effects on 5-HT and c-Fos IR were partially prevented by pre-treatment with 8-OH-DPAT.

Conclusion: 

LC neurons and especially ascending 5-HT neurons from the dorsal raphe play a crucial role in mediating the beneficial effects of the 5-HT_1A agonist 8-OH-DPAT in LH, resulting in a partial prevention of the detrimental effects of immobilization on the avoidance and escape responses.