Male Flinders Sensitive Line Rats Research Articles

Olfactory discrimination and memory deficits in the Flinders Sensitive Line rodent model of depression

Major Depressive Disorder (MDD) is a heterogeneous psychiatric disorder with broad symptomatic manifestations. The current study examined, for the first time, olfactory memory and discrimination in the Flinders Sensitive Line (FSL) rodent model of depression. Male FSL rats and controls were trained on an Olfactory Discrimination (OD) and a Social Interaction (SI) test. On the OD test, the FSL and controls performed similarly at the shortest inter-trial interval (5min), however, with extended delay of 30min, the FSLs had a recall and odour discrimination deficit. At the longest delay (60min) both groups performed poorly. The FSL rats i.) had a deficit in olfactory discrimination suggesting impairment in olfactory memory and recall; ii.) were less likely to socialize with unfamiliar rats. The data suggests that FSL animals have an impaired olfactory information processing capacity.

Head shaking in the forced swim test: A robust but unexplored sex difference

Preclinical psychopharmacology research needs novel behavioral indices and improved animal models for both sexes. The forced swim test (FST) is the most popular test for screening antidepressant potential. Sex differences in FST behaviors, such as immobility and swimming, are not consistent among laboratories. Reliable indices, sensitive to sex differences, are required. We identified a robust sex difference in the frequency of headshakes during the standard two session FST, with male rats exhibiting higher number of head shakes than females. Furthermore, we explored whether strain, ageing, sex- and stress-hormone levels influence this sex difference. Experiments in middle-aged and senescent Wistar rats, as well as in gonadectomized and adrenalectomized with corticosterone replacement young adult males and females, revealed that sex differences in headshakes during FST are not influenced by age or corticosterone, but are abolished following castration of male rats. Interestingly, headshake frequency correlated positively with testosterone, but not corticosterone levels. Finally, testing of Flinders Sensitive Line (FSL) and Sprague-Dawley (SD) rats in a single 5min FST session revealed that headshake frequency is sensitive to antidepressant treatment with female rats exhibiting opposite responses to treatment than male FSL rats. Mirtazapine, a 5-HT2 antagonist, enhanced headshakes in females and decreased them in male FSL rats. Based on current data and the available literature, sex differences in headshake frequency should be linked to analogous sex differences in serotonin receptors. Headshake frequency during the FST is an additional valuable behavioral index, sensitive to sex differences, gonadal hormones and antidepressants modulating serotonin receptors.

Citalopram-mediated anxiolysis and differing neurobiological responses in both sexes of a genetic model of depression

Disorders such as depression and anxiety exhibit strong sex differences in their prevalence and incidence, with women also differing from men in their response to antidepressants. Furthermore, receptors for corticotrophin releasing hormone (CRHR1) and arginine vasopressin receptor subtype 1b (AVPR1b) are known to contribute to the regulation of mood and anxiety. In the present study, we compared the anxiety profile and CRHR1 and AVPR1b expression levels in control Sprague-Dawley (SD) rats and rats of the SD-derived Flinders Sensitive Line (FSL), a genetic model of depression. Additionally, given the apparent sex differences in the therapeutic efficacy of antidepressants and because antidepressants are commonly used to treat comorbid anxiety and depressive symptoms, we assessed whether the anxiolytic effects of an antidepressant occur in a sex-dependent manner. Male and female FSL rats were treated with citalopram 10 mg/kg once daily for 14 days and were then tested in the open field and the elevated plus maze paradigms. Upon completion of the behavioural analysis, AVPR1b and CRHR1 expression levels were monitored in the hypothalamus and the prefrontal cortex (PFC) using Western blotting. According to our results, male FSL rats were more anxious than control SD rats, a difference abolished by citalopram treatment. Baseline anxiety levels were similar in female FSL and SD rats, and citalopram further reduced anxiety in female FSL rats. Importantly, whereas citalopram altered AVPR1b expression in the hypothalamus of male FSL rats, its actions on this parameter were restricted to the PFC in female FSL rats. In both sexes of FSL rats, citalopram did not alter CRHR1 expression in either the hypothalamus or PFC. Our results demonstrate that antidepressant treatment reduces anxiety levels in FSL rats of both sexes: the magnitude of treatment effect was related to the starting baseline level of anxiety and the antidepressant elicited sexually differentiated neurobiological responses in specific brain regions.

Depressive Characteristics of FSL Rats: Involvement of Central Nicotinic Receptors

Antidepressant effects of acute or chronic nicotine treatments in swim test immobility of Flinders sensitive line (FSL) rats, an animal model of depression, were recently demonstrated (Tizabi et al. Psychopharmacology 142:193, 1999). In the present study we sought to determine whether the antidepressant effects of nicotine could be blocked by the nicotinic antagonist, mecamylamine (MEC). Moreover, the effects of chronic nicotine treatment on [ 3H]cytisine binding in discrete brain regions of FSL and their control Flinders resistant line (FRL) rats were also evaluated. Adult male FSL rats were treated with MEC (0.5 mg/kg) 20 min prior to an acute or chronic nicotine administration. MEC by itself did not affect the immobility in swim test. However, it completely blocked the acute or chronic nicotine effects. Daily nicotine injection (0.4 mg/kg/day for 14 days) resulted in an increase in [ 3H]cytisine binding primarily in the FRL rats. An increase in nicotinic receptor binding following chronic nicotine administration is believed to reflect desensitization of these receptors. These findings, coupled with previous observation of higher basal nicotinic receptors in FSL rats, further support the involvement of central nicotinic receptors in depressive characteristics of these rats. Moreover, the data suggest therapeutic potential for selective nicotinic receptor agonists in depressive disorders.