Sexually dimorphic responses of rats to fluoxetine in the forced swimming test are unrelated to the function of the serotonin transporter in the brain.

Due to the prevalence of depression in women, female rats may be a better models for antidepressant research than males. In male rats, fluoxetine inhibited the serotonin (5-hydroxytryptamine, 5-HT) transporter (SERT) which is reducing the immobility time in the repeated forced swimming test (rFST). The performance of female rats in this test is unknown. In this study, responses of male and female rats in the rFST under chronic treatment with fluoxetine and the function of SERT in their brains were examined. Wistar rats received oral fluoxetine (females: 0, 1, 2.5, or 5 mg kg-1  day-1 ; males: 0 or 2.5 mg kg-1  day-1 ; in sucrose 10%, 1.5 ml/rat) 1 hr before the test daily for 12 days over the course of the rFST. rFST consisted of a 15 min pretest followed by 5 min sessions of swimming at 1 (test), 7 (retest 1), and 14 (retest 2) days later. SERT functioning was assessed by ex vivo assays of the frontal cortex and hippocampus of rats. Fluoxetine reduced immobility time of males in the rFST while it failed to do so in females. In vitro treatment with fluoxetine inhibited the uptake of 5-HT of both sexes similarly, while in vivo chronic administration of fluoxetine failed to do so. In summary, rats responded to the chronic treatment with fluoxetine in a sexually dimorphic fashion during the rFST despite the functioning of SERT in their brains remaining equally unchanged. Hence, our data suggest that sexually dimorphic responses to fluoxetine in rFST may be unrelated to the function of SERT in rat brains.

Repeated forced-swimming test in intact female rats: behaviour, oestrous cycle and enriched environment.

Psychopharmacology used animal models to study the effects of drugs on brain and behaviour. The repeated forced-swimming test (rFST), which is used to assess the gradual effects of antidepressants on rat behaviour, was standardized only in males. Because of the known sex differences in rats, experimental conditions standardized for males may not apply to female rats. Therefore, the present work aimed to standardize experimental and housing conditions for the rFST in female rats. Young or adult Wistar female rats were housed in standard or enriched environments for different experimental periods. As assessed in tested and nontested females, all rats had reached sexual maturity by the time behavioural testing occurred. The rFST consisted of a 15-min session of forced swimming (pretest), followed by 5-min sessions at 1 (test), 7 (retest 1) and 14 days (retest 2) later. The oestrous cycle was registered immediately before every behavioural session. All sessions were videotaped for further analysis. The immobility time of female rats remained similar over the different sessions of rFST independent of the age, the phase of the oestrous cycle or the housing conditions. These data indicate that rFST in female Wistar rats may be reproducible in different experimental conditions.

Failure to detect the action of antidepressants in the forced swim test in Swiss mice.

OBJECTIVE: The aims of this study were to replicate previously published experiments and to modify the protocol to detect the effects of chronic antidepressant treatment in mice. METHODS: Male Swiss mice (n=6-8/group) housed in reversed light/dark cycle were randomly assigned into receive vehicle (10% sucrose), sub-effective doses (1 and 3 mg/kg) or effective doses (10 and 30 mg/kg) of bupropion, desipramine, and fluoxetine and a candidate antidepressant, sodium butyrate (1-30 mg/kg) per gavage (p.o.) 1 h before the forced swim test (FST). Treatments continued daily for 7 and 14 days during retests 1 and 2, respectively. In an additional experiment, mice received fluoxetine (20 mg/kg) or vehicle (10% sucrose or 0.9% saline) p.o. or i.p. before the FST. Mice housed in reversed or standard light/dark cycles received fluoxetine (20 mg/kg) prior FST. Video recordings of behavioural testing were used for blind assessment of the outcomes. RESULTS: According to the expected, doses of antidepressants considered sub-effective failed to affect the immobility time of mice in the FST. Surprisingly, acute and chronic treatment with the high doses of bupropion, desipramine, and fluoxetine or sodium butyrate also failed to reduce the immobility time of mice in the FST. Fluoxetine 20 mg/kg was also ineffective in the FST when injected i.p. or in mice housed in normal light/dark cycle. CONCLUSION: Data suggest the lack of efficacy of orally administered bupropion, desipramine, fluoxetine in the FST in Swiss mice. High variability, due to high and low immobility mice, may explain the limited effects of the treatments.

A subiculum-hypothalamic pathway functions in dynamic threat detection and memory updating.

Animals need to detect threats, initiate defensive responses, and, in parallel, remember where the threat occurred to avoid the possibility of re-encountering it. By probing animals capable of detecting and avoiding a shock-related threatening location, we were able to reveal a septo-hippocampal-hypothalamic circuit that is also engaged in ethological threats, including predatory and social threats. Photometry analysis focusing on the dorsal premammillary nucleus (PMd), a critical interface of this circuit, showed that in freely tested animals, the nucleus appears ideal to work as a threat detector to sense dynamic changes under threatening conditions as the animal approaches and avoids the threatening source. We also found that PMd chemogenetic silencing impaired defensive responses by causing a failure of threat detection rather than a direct influence on any behavioral responses and, at the same time, updated fear memory to a low-threat condition. Optogenetic silencing of the main PMd targets, namely the periaqueductal gray and anterior medial thalamus, showed that the projection to the periaqueductal gray influences both defensive responses and, to a lesser degree, contextual memory, whereas the projection to the anterior medial thalamus has a stronger influence on memory processes. Our results are important for understanding how animals deal with the threat imminence continuum, revealing a circuit that is engaged in threat detection and that, at the same time, serves to update the memory process to accommodate changes under threatening conditions.

Bibliometric trend analysis of non-conventional (alternative) therapies in veterinary research.

Background: There is an increased interest in Non-Conventional Therapies (NCTs), often referred to as complementary and alternative medicines, in veterinary clinical practice.Aim: To map the bibliometric outputs of NCTs in veterinary medicine, and identify which are most prevalent, and the extent to which their publishing has increased.Methods: Text mining algorithms were applied to detect 17 NCTs-related terms (acupuncture, ayurveda/ayurvedic, traditional Chinese medicine, traditional medicine, chiropractic, electroacupuncture, essential oil, plant extract, ethnopharmacology, herbal medicine, homeopathy, low-level laser therapy, medicinal plant, natural product, osteopathy, phytotherapy, and massage) in the title, abstract or keywords of all retrievable literature until 2020 under the PubMed MeSH term 'veterinary' (N = 377 556). Point prevalence, incidence by decade and cumulative incidence were calculated.Results: Bibliometric trend analysis revealed an overall increase in NCTs-related terms over the last 20 years, with a substantial growth of studies mentioning plant extracts, essential oils and medicinal plants. Traditional Chinese medicine, herbal medicine and natural product have also increased in the same period, although their numbers remain low. Conversely, reference to acupuncture has decreased in the last decade when compared with the previous decade, whereas references to homeopathy, electroacupuncture, osteopathy and chiropractic remained scarce, suggesting that their use in veterinary clinical practice may not be based on published evidence.Conclusion: Further reviews to explore this issue are warranted, differentiating secondary from primary literature, and assessing relevance and methodological quality of individual studies, following the principles of evidence-based veterinary medicine.