Neuroscience Letters 412 (2007) 84–88 5-HT 1A receptor activation counteracted the effect of acute immobilization of noradrenergic neurons in the rat locus coeruleus Jos´ e Rioja a,c , Luis J. Sant´ ın b , Diana L ´ opez-Barroso b , Alicia Do ˜ na a , Eugenia Ulzurrun c , Jos´ e A. Aguirre a,∗ a Department of Human Physiology, School of Medicine, University of M´ alaga, 29071 M´ alaga, Spain b Department of Psychobiology, School of Psychology, University of M´ alaga, 29071 M´ alaga, Spain c Medical Research Centre (CIMES). Department of Medicine, University of M´ alaga, 29071 M´ alaga, Spain Received 25 June 2006; received in revised form 11 September 2006; accepted 3 October 2006 Abstract The aim of our study was to evaluate the effect of acute stress and the 5-HT 1A receptor involvement in both, the hippocampus noradrenaline (NA) tissue levels and the c-Fos immunoreactivity (c-Fos-IR) in the catecholaminergic neurons of the locus coeruleus (LC). Double immunocytochemical staining of tyrosine hydroxilase (TH) and c-Fos protein combined with stereological techniques were used to study the specific cell activation in the LC neurons in five experimental groups (control group, immobilization (1h) group, 8-OH-DPAT group (8-OH-DPAT 0.3mg/kg, s.c.), DPAT+IMMO group (8-OH-DPAT 0.3mg/kg, s.c., 30 ′ prior acute immobilization) and WAY+DPAT+IMMO group (WAY-100635 0.3mg/kg, s.c. and 8-OH-DPAT 0.3mg/kg, s.c., 45 ′ and 30 ′ , respectively, before immobilization). The results showed that hippocampal NA tissue levels and c-Fos-IR in the TH positive neurons of the LC were significantly increased immediately and after 90 ′ , respectively, after the immobilization period. Pre-treatment with 8-OH-DPAT counteracted the effects induced by immobilization, but pre-treatment with WAY-100635 did not block the effects induced by 8-OH-DPAT. These results suggest that noradrenaline system is associated in a significant way with immobilization stress. The role of 5-HT 1A receptor activation in this stress response is also discussed. © 2006 Published by Elsevier Ireland Ltd. Keywords: Immobilization stress; Locus coeruleus; Hippocampus; c-Fos immunohistochemistry; Noradrenaline; 5-HT 1A receptor Exposure to uncontrollable stressors may develop psychopatho- logic disorders such as panic, mood swings and anxiety. The hypothesis that the stress response courses with a mediated relationship between serotonergic and catecholaminergic cen- tral systems [4] focused attention on the interaction between the locus coeruleus nucleus (LC) and the dorsal raphe nucleus (DR) demonstrating a reciprocal control between both nuclei [25]. The serotonin released from the DR nucleus may control the firing activity of noradrenergic neurons of the LC via postsinap- tic somatodendritic 5-HT 1A receptor activation [25]. In keeping with this hypothesis, it has been demonstrated that the stim- ulation of 5-HT 1A autoreceptors in the DR nucleus induces a decreased noradrenaline (NA) release in this nucleus from the ∗ Corresponding author at: Department of Human Physiology, School of Medicine, Campus de Teatinos, Boulevard Louis Pasteur 32, University of M´ alaga, 29071 M´ alaga, Spain. Tel.: +34 952 134212; fax: +34 952 131650. E-mail address: Jose.Aguirre@uma.es (J.A. Aguirre). LC [18]. On the other hand, the LC also displays an impor- tant control on the activity of both dorsal and median raphe nuclei, with a NA release via stimulation of  1 -somatodentritic adrenoceptors located in the hindbrain raphe nuclei, activating the serotonin release. In this way, electron microscopy [1] and retrograde tracing [22,23] have demonstrated a rich noradren- ergic innervation of the DR nucleus arising from the LC. Thus, clonidine infusions in the brain leads to an important inhibition of the firing rate of the LC neurons with a subsequent decrease in extracellular NA levels in both LC and DR, being reduced the serotonin release by 80% in the former nucleus [18]. We have previously reported that 5-HT 1A receptor activation coun- teracts the increased activation of serotonergic neurons in the dorsal and median raphe nuclei under acute stress of immobiliza- tion [19]. Furthermore, immobilization courses with increased serum corticosterone levels [20] that strongly increase the affin- ity of the 5-HT 1A receptors in the DR [2] and also mediate in the induced long-term behavioural effects [8,9], including pas- sive avoidance [20]. Dorsal ascending noradrenergic bundle [12] 0304-3940/$ – see front matter © 2006 Published by Elsevier Ireland Ltd. doi:10.1016/j.neulet.2006.10.013