RESUMO
The Wistar Hannover rat (WHR) is a strain commonly used for toxicity studies but rarely used in studies investigating depression neurobiology. In this study, we aimed to characterise the behavioural responses of WHR to acute and repeated antidepressant treatments upon exposure to the forced swim test (FST) or learned helplessness (LH) test. WHR were subjected to forced swimming pre-test and test with antidepressant administration (imipramine, fluoxetine, or escitalopram) at 0, 5 h and 23 h after pre-test. WHR displayed high immobility in the test compared to unstressed controls (no pre-swim) and failed to respond to the antidepressants tested. The effect of acute and repeated treatment (imipramine, fluoxetine, escitalopram or s-ketamine) was then tested in animals not previously exposed to pre-test. Only imipramine (20 mg/kg, 7 days) and s-ketamine (acute) reduced the immobility time in the test. To further investigate the possibility that the WHR were less responsive to selective serotonin reuptake inhibitors, the effect of repeated treatment with fluoxetine (20 mg/kg, 7 days) was investigated in the LH model. The results demonstrated that fluoxetine failed to reduce the number of escape failures in two different protocols. These data suggest that the WHR do not respond to the conventional antidepressant treatment in the FST or the LH. Only s-ketamine and repeated imipramine were effective in WHR in a modified FST protocol. Altogether, these results indicate that WHR may be an interesting tool to investigate the mechanisms associated with the resistance to antidepressant drugs and identify more effective treatments.
Assuntos
Fluoxetina , Imipramina , Ratos , Animais , Fluoxetina/farmacologia , Ratos Wistar , Imipramina/farmacologia , Imipramina/uso terapêutico , Depressão/tratamento farmacológico , Escitalopram , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Natação , Comportamento Animal , Modelos AnimaisRESUMO
Peripheral chemoreflex is activated during short-term sustained hypoxia (SH), and the first synapse of these afferents is located in Nucleus Tractus Solitarius(NTS). NTS neurons projecting to the ventral lateral medulla (NTS-VLM) are part of the respiratory pathways of the chemoreflex. SH increases the magnitude of basal respiratory parameters in rats from Wistar-Hannover strain. In this study, we hypothesized that the observed changes in the respiratory pattern in response to SH were due to changes in the GABAergic modulation of the synaptic transmission of NTS-VLM neurons. We used an electrophysiological approach to record the synaptic activity of NTS neurons labeled with a retrograde tracer previously microinjected into VLM of Wistar-Hannover rats submitted to 24â¯h SH. The data are showing that: (a) the amplitude of evoked inhibitory currents in NTS-VLM neurons of SH rats was reduced and not accompanied by any change in rise-time and decay-time; (b) the 1/CV2 and the number of failures in response to evoked currents were also affected by SH; (c) the frequency of spontaneous inhibitory currents was reduced by SH without changes in amplitude and half-width. These effects of SH were observed in NTS-VLM neurons located in caudal and intermediate NTS, but not in NTS-VLM neurons located in the rostral NTS. We conclude that SH causes a reduction in inhibitory modulation onto NTS-VLM neurons by pre-synaptic mechanisms, which may contribute to the observed changes in the respiratory pattern of Wistar-Hannover rats submitted to SH.