Hormonal and cognitive factors associated with the exploratory behavior of rats submitted to repeated sessions of the elevated plus-maze.

Abstract

Naive rats submitted to the elevated plus-maze (EPM) display a characteristic increase in open arm exploration and reduced risk assessment behaviors (RABs) after the administration of anxiolytic drugs. Upon re-exposure to the maze, however, the traditional measures of the EPM become resistant to these drugs. This intriguing phenomenon was initially observed for the benzodiazepine chlordiazepoxide and referred as one-trial tolerance (OTT). In this review, we summarized hormonal, cognitive and neuroanatomical data obtained from rats submitted to the test/retest protocol in the EPM. The re-exposure to the EPM is characterized by more prominent RABs and a distinct Fos protein distribution in the brain, particularly in limbic structures involved with the cognitive aspects of fear, such as the ventral regions of the medial prefrontal cortex (mPFC) and amygdala. Interestingly, naive rats treated with midazolam had a significant decrease in the number of Fos-positive neurons in the anterior cingulate cortex, area 1 (Cg1), anterior and dorsal premammillary nuclei of hypothalamus. On the other hand, midazolam caused a significant decrease in the number of Fos-positive neurons in the mPFC, amygdala, dorsomedial nucleus of hypothalamus and raphe nuclei in maze-experienced rats. Cg1 was the only structure targeted by the benzodiazepine in both sessions. Systemically administered midazolam before test or retest sessions reduced the RABs and plasma corticosterone levels in rats submitted to both sessions. Similar behavioral results were obtained with intra-Cg1 infusions of midazolam. The results reviewed here support the view of the crucial role of the RABs in the development of the OTT and point to this mPFC area as an important locus for the anxiolytic-like action of benzodiazepines in rodents.

Yohimbine anxiogenesis in the elevated plus maze requires hindbrain noradrenergic neurons that target the anterior ventrolateral bed nucleus of the stria terminalis

“…Those authors also reported distinct behaviors displayed by rats during initial and subsequent EPMZ exposure that are associated with distinct patterns of brain activity. For example, maze‐experienced rats display significantly more neuronal cFos activation within the ventral mPFC, BLA and central amygdala after EPMZ re‐testing compared with cFos activation displayed by maze‐naïve rats after initial testing (Albrechet‐Souza et al ., ; Albrechet‐Souza & Brandao, ). It has been suggested that the reduced exploratory behavior and open arm activities displayed by rats during maze re‐exposure is indicative of learned avoidance, and can be used to assess memory acquisition and retention (Bertoglio & Carobrez, , ; Albrechet‐Souza & Brandao, ; Galvis‐Alonsoa et al ., ).…”

“…saline, and further demonstrated that DSAP lesions did not alter the known effect of prior EPMZ experience to alter EPMZ behavior during a subsequent test, a phenomenon observed previously in non‐lesioned rats (File et al ., , ; Treit et al ., ; Bertoglio & Carobrez, , ; Albrechet‐Souza & Brandao, ). Indeed, test/retest EPMZ data in the present study are very similar to data reported by Albrechet‐Souza & Brandao (, see their Fig. B).…”

“…For example, maze-experienced rats display significantly more neuronal cFos activation within the ventral mPFC, BLA and central amygdala after EPMZ re-testing compared with cFos activation displayed by maze-na € õve rats after initial testing (Albrechet-Souza et al, 2008;Albrechet-Souza & Brandao, 2010). It has been suggested that the reduced exploratory behavior and open arm activities displayed by rats during maze re-exposure is indicative of learned avoidance, and can be used to assess memory acquisition and retention (Bertoglio & Carobrez, 2000, 2004Albrechet-Souza & Brandao, 2010;Galvis-Alonsoa et al, 2010). In the present study, DSAP lesions had no significant impact on the development of avoidance learning that presumably underlies the qualitative shift in emotional state suggested by behavioral changes between Test 1 and Test 2.…”

“…In a second experiment, we examined whether loss of vlBST-projecting NA neurons alters the pronounced effect of prior maze experience to alter maze behavior during a subsequent test, a phenomenon observed previously in non-lesioned rats (File et al, 1990(File et al, , 1993Treit et al, 1993;Bertoglio & Carobrez, 2000, 2004Albrechet-Souza & Brandao, 2010). It has been suggested that the reduced exploratory behavior and open arm activities displayed by rats during maze re-exposure is indicative of learned avoidance, and can be used to assess memory acquisition and retention (Bertoglio & Carobrez, 2000, 2004Albrechet-Souza & Brandao, 2010;Galvis-Alonsoa et al, 2010). Therefore, we sought to determine whether vlBST-projecting NA neurons participate in this process of emotional learning and memory.…”

“…The first experiment compared the effects of systemic YO and vehicle treatment on EPMZ behavior in sham control and lesioned rats. In a second experiment, we examined whether loss of vlBST‐projecting NA neurons alters the pronounced effect of prior maze experience to alter maze behavior during a subsequent test, a phenomenon observed previously in non‐lesioned rats (File et al ., , ; Treit et al ., ; Bertoglio & Carobrez, , ; Albrechet‐Souza & Brandao, ). It has been suggested that the reduced exploratory behavior and open arm activities displayed by rats during maze re‐exposure is indicative of learned avoidance, and can be used to assess memory acquisition and retention (Bertoglio & Carobrez, , ; Albrechet‐Souza & Brandao, ; Galvis‐Alonsoa et al ., ).…”