ABSTRACT
Antidepressant treatment attenuates behavioral changes induced by uncontrollable stress. The periaqueductal gray matter (PAG) is proposed to be a brain site involved in the behavioral responses to uncontrollable stress and antidepressant effects. The main goal of the present study was to investigate the effect of antidepressant treatment on the pattern of neural activation of the PAG along its mediolateral and rostrocaudal subregions after a forced swim stress episode. Male Wistar rats were sub-acutely treated with desipramine (a selective noradrenaline re-uptake blocker, three injections of 10 mg/kg in 24 h) or clomipramine (a non-selective serotonin and noradrenaline re-uptake blocker, three injections of 10 mg/kg in 24 h) and submitted to the forced swimming test (FST). Two hours after the test their brain were removed for Fos immunohistochemistry. Fos-like immunoreactivity (FLI) in rostral, intermediate and caudal portions of dorsomedial (dmPAG), dorsolateral (dlPAG), lateral (lPAG) and ventrolateral (vlPAG) PAG were quantified by a computerized system. The FST session increased FLI in most parts of the PAG. Previous treatment with desipramine or clomipramine reduced FLI in all columns of the PAG. FLI in the PAG correlated positively with to the immobility time and negatively with to climbing behavior scored during the test. These results indicate that neurons in the PAG are activated by uncontrollable stress. Moreover, inhibitory action of antidepressants on this activity may be associated with the anti-immobility effects of these drugs in the FST.
Subject(s)
Antidepressive Agents/therapeutic use , Clomipramine/therapeutic use , Desipramine/therapeutic use , Oncogene Proteins v-fos/metabolism , Periaqueductal Gray/drug effects , Stress, Psychological/drug therapy , Analysis of Variance , Animals , Cell Count/methods , Disease Models, Animal , Immobility Response, Tonic/drug effects , Male , Periaqueductal Gray/pathology , Rats , Rats, Wistar , Stress, Psychological/etiology , Swimming/psychologyABSTRACT
Forced swimming test (FST) or 'behavioural despair' test is a useful screening for antidepressant drugs. The FST predictability has been improved by a number of procedural modifications. Description of the behavioural microstructure in FST may help to delineate innovative protocols. Thus, counts of all behaviours emitted during FST in rats (four-month-old Wistar male, n = 63) were recorded and examined by Markovian sequential analysis (MSA) and principal components analysis (PCA). In a second experiment, rats (n = 28) were tested in an open field test (OFT) followed a week later by FST; behaviours in both tests were recorded and analysed by two correlation methods (Pearson's test and sliding window correlation). The descriptive ethological analysis displayed counts of swimming and immobility increased over the course of the test, whereas climbing behaviour decreased. The MSA revealed the occurrence of immobility was predicted by swimming, climbing, and diving behaviours whereas the immobility predicted the occurrence of swimming behaviour and headshakes. The PCA showed duration of immobility and climbing loaded into one component and duration of immobility and swimming loaded into another one. Low as well high levels of climbing behaviour were positively correlated with motor activity in the OFT. In brief, the present data suggest there are at least two different factors that grouped variables related to the behavioural despair in the FST. In addition, altered motor activity could be predicted by the frequency of climbing behaviour recorded in the FST.
