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The 5-HT2B/2C receptor antagonist SB 206553 exerts anxiolytic effects in rat models of anxiety. However, these effects have been reported for standard rat strains, thus raising the issue of SB 206553 effects in rat strains displaying different levels of anxiety. Herein, the effects of SB 206553 in a 5-min elevated plus-maze test of anxiety were compared to those of the reference anxiolytic, diazepam, in two rat strains respectively displaying high (Lewis rats) and low (spontaneously hypertensive rats, SHR) anxiety. Diazepam (0.37, 0.75, or 1.5 mg/kg; 30 min before testing) increased in a dose-dependent manner the behavioral measures in SHR, but not in Lewis rats. On the other hand, SB 206553 (1.25, 2.5, or 5 mg/kg; 30 min before testing) failed to alter the anxiety parameters in both strains, whereas it increased closed arm entries in Lewis rats, suggesting that it elicited hyperactivity in the latter strain. Accordingly, the hypolocomotor effect of the nonselective 5-HT2B/2C receptor agonist m-chlorophenylpiperazine (1.5 mg/kg ip 20 min before a 15-min exposure to an activity cage) was prevented by the 1.25 and 2.5 mg/kg doses of SB 206553 in Lewis rats and SHR, respectively. Compared with SHR, Lewis rats may display a lower response to benzodiazepine-mediated effects and a more efficient control of locomotor activity by 5-HT2B/2C receptors.

There is evidence for stressor- and brain region-specific selectivity in serotonergic transmission responses to aversive stimuli. The aim of the present review is to provide an overview of the effects of different acute and repeated/chronic stressors on serotonin (5-HT) release and reuptake, extracellular 5-HT levels, and 5-HT pre- and postsynaptic receptors in areas tightly linked to the control of fear and anxiety, namely the dorsal and median raphe nuclei, the frontal cortex, the amygdala and the hippocampus. In addition, our knowledge of the impacts of corticoids on serotonergic systems in these brain areas is also briefly provided to examine whether the hypothalamo-pituitary-adrenal axis may play a role in stress-induced alterations in 5-HT neurotransmission. Taken together, the data presented reinforce the hypothesis that stress affects such a transmission, partly through the actions of corticoids. However, we are still left with unanswered, albeit crucial questions. First, the question of the specificity of the serotonergic responses to stress, with regard to the site of action and the nature of the stressor still remains open due to the heterogeneity of the results obtained so far. This could indicate that environmental factors, other than the stressor itself, may have enduring consequences on 5-HT sensitivity to stress. Second, the question regarding the role of stress-elicited changes in 5-HT transmission within coping processes finds in most cases no clearcut answer. In keeping with human symptomatology, the need to consider the environment (including the early one) and the genetic status when assessing the effects of stress on 5-HT neurotransmission is underlined. Such a consideration could help to answer the questions raised. [ABSTRACT FROM AUTHOR]

Anorexia nervosa (AN), mostly observed in female adolescents, is the most fatal mental illness. Its core is a motivational imbalance between exercise and feeding in favour of the former. Although several animal models of AN have been proposed, none of them specifically assesses the motivation for exercise and/or feeding. In keeping with this issue, we recently developed an operant conditioning-based model wherein motivation for each of these two rewards can be examined singly or within a choice setting in mice [1]. By means of this model, we have recently examined whether infant-early adolescent stress (post-weaning social isolation), one precipitating factor in AN, affects in a sex-dependent manner the reinforcing values of either reward [2]. Stressed and control male/female C57Bl/6 N mice were exposed, when 5-weeks old, to a cued-reward motivated instrumental task wherein wheel-running sequences and palatable food pellets, each reward provided singly, were conditioned by nose-poke responses. These responses obeyed fixed ratio (FR) reinforcement schedules for 10 sessions before being tested under a progressive ratio (PR) schedule of reinforcement for one session. Thereafter, mice underwent 10 FR sessions wherein they had the choice between either reward, the last 5 sessions being performed under food restriction conditions. Infant-adolescent stress, which began at postnatal day 22 (first postweaning day), consisted in individual housing, as compared to controls, which were all collectively housed (3/cage). Whether wheel-running and palatable food were provided separately or within a choice paradigm, post-weaning isolation-reared males responded to similar extents for each reward when the three other mouse groups displayed increased responding for wheel-running. The negative impact of the early stressor on male nose poke responding for wheel-running, compared to that measured in the other mouse groups, extended to the running performance during each rewarded sequence (i.e. reward consumption). When food-restricted, motivation for food overpassed progressively that for running in all groups, with females reaching higher levels than males. Although the stress model that we used did not trigger a sex-dependent imbalance between exercise and feeding drives that would be reminiscent of what is observed in anorectic girls, we believe that the quest for other stress models, possibly combined with genetics, could prove fruitful to model some endophenotypic traits of AN. [ABSTRACT FROM AUTHOR]