The aim of the present study was to strengthen our hypothesis of a common physiological basis for post-traumatic stress disorder (PTSD) and substance use disorders. This paper investigates the ...possibility that rats exposed to a PTSD model exhibit noradrenergic and behavioral sensitization, as observed following repeated drugs of abuse injections. First, rats received a single prolonged stress (SPS), combining three consecutive stressors. They were then tested, 2 weeks after the trauma for PTSD-like symptoms to discriminate between vulnerable and resilient rats. When microdialysis was performed in the prelimbic cortex (Experiment 1), larger increases of noradrenaline (NA) release in response to amphetamine were observed in vulnerable rats when compared to control and resilient animals. Experiment 2 showed that trauma-vulnerable rats exhibited increases in locomotor activity relative to controls, in response to an exposure to trauma-associated cues. These data demonstrate that a single trauma exposure induces in vulnerable animals both, a noradrenergic sensitization evidenced within the prelimbic cortex and behavioral sensitization obtained after a physiologic activation of the noradrenergic system. However, Experiment 3 showed that when NA system was activated by amphetamine (1 mg/kg), a decrease in behavioral sensitization was obtained in vulnerable rats. We proposed that this decreased locomotor activity results from an additional stress-induced increased reactivity of mesocortical dopaminergic neurons, known to counteract the consequences of cortical noradrenergic release in rats. These results support our hypothesis that noradrenergic sensitization represents a common physiological basis, involved both in PTSD and drug addiction and suggest new common therapeutic approaches for these pathologies.
Rats trained in a dual-solution cross-maze task, which can be solved by place and response strategies, predominantly used a response strategy after extensive training. This paper examines the ...involvement of the medial and lateral dorsal striatum (mDS and lDS) in the choice of these strategies after partial and extensive training. Our results show that rats with lDS and mDS lesions used mainly a response strategy from the early phase of training. We replicated these unexpected data in rats with lDS lesions and confirmed their tendency to use the response strategy in a modified cross-maze task. When trained in a dual-solution water-maze task, however, control and lesioned rats consistently used a place strategy, demonstrating that lDS and mDS lesioned rats can use a place strategy and that the shift towards a response strategy did not systematically result from extensive training. The present data did not show any clear dissociation between the mDS and lDS in dual solution tasks. They further indicate that the dorsal striatum seems to determine the strategies adopted in a particular context but cannot be considered as a neural support for the response memory system. Accordingly, the role of the lateral and medial part of the dorsal striatum in egocentric/response memory should be reconsidered.
Abstract In this study, we investigated long-term repercussion of early glutathione deficit by l -buthionine-(S,R)-sulfoximine (BSO) injections as a rat model of schizophrenia. BSO rats were tested ...through various behavioral tasks requiring animals to take into account previously delivered information. We showed that relative to controls, BSO rats (1) were less active and more anxious in an Elevated Plus Maze test, allowing us to split them into two subgroups with high and low anxiety levels; (2) demonstrated normal abilities of behavioral flexibility tested with a rat-adapted version of the Wisconsin Card Sorting Test (WCST), with even higher abilities in anxious BSO rats suggesting reduced interference of previously acquired rules; (3) did not forage normally in radial arm mazes and mainly used clockwise strategies; (4) exhibited a lack of habituation during a startle response task; and (5) showed a normal prepulse inhibition of the startle response (PPI) and a normal conditioned taste aversion (CTA). All these results indicate that early glutathione deficit provokes persistent changes in adulthood and improves the validity of this animal model of schizophrenia. They further suggest difficulties binding temporally separated events (WCST), except when the salience of this information is very strong (CTA). We propose that the transient glutathione deficit during cerebral development could alter a “cognitive binding” process in interaction with the emotional state that could possibly account for the disruption of integrative function that characterizes schizophrenia.
Abstract Low concentrations of n-3 polyunsaturated fatty acid (PUFA) and chronic stress are implicated in susceptibility to mood disorders. We have investigated the combined effects of chronic n-3 ...PUFA dietary deficiency and early maternal separation (MS) stress on the reactivity to stressful situations of rats as adults. Pups fed a control or an n-3 PUFA deficient diet were daily separated for two weeks before weaning They were all tested at 3 month-old to determine their anxiety, and their ability to learn two aversive tasks differing in the control they could exert on the situation: auditory fear conditioning and brightness avoidance discrimination. Neither the n-3 PUFA-deficient diet nor MS alone significantly affected behavior. But n-3 PUFA-deficient rats that had been separated were more anxious and fearful in inescapable situations, while their ability to cope with an aversive avoidance task remained unaffected. These results support the notion that PUFA-unbalanced diet, together with stress, may be a determinant risk factor in emotional disorders.
Rationale
The aim of this paper is to provide evidence for the hypothesis that posttraumatic stress disorder (PTSD) and drug addiction rely on common processes.
Objective
Our objective is to show ...that a noradrenergic-dependent behavioral sensitization occurs after the development of PTSD, in a way similar to that recently demonstrated after repeated drug injections.
Methods
Rats classified into high and low responders to novelty (HR/LR) were subjected to a single prolonged stress (SPS). Cross-sensitization was evaluated after d-amphetamine injection (1.0 mg/kg) in a locomotor activity test given either 4, 15, or 90 days later. To determine the involvement of the noradrenergic system, rats were injected with the α2-receptor agonist, clonidine (20 μg/kg), during the SPS. Subsequently, their auditory startle response (ASR) and cross-sensitization were assessed.
Results
SPS affected both the hypothalamic–pituitary–adrenal axis and the ASR, replicating some PTSD-like symptoms. Behavioral sensitization was found after 15, 21, and 90 days after the SPS in LR rats, and a behavioral desensitization in HR rats after 15 days. Clonidine delivered during the SPS prevented the behavioral sensitization in LR rats, as well as the effects on ASR in HR and LR rats.
Conclusions
Exposure to SPS is shown to affect behavior and induce a behavioral sensitization to d-amphetamine that is modulated by individual differences. Both of these effects depend on the noradrenergic system. Altogether, the present results (1) replicate findings obtained after repeated drug exposure and (2) strengthen our hypothesis of a common physiological basis between PTSD and drug addiction.
Commentary: Rehebbilitating Memory Gisquet-Verrier, Pascale; Riccio, David C
Frontiers in behavioral neuroscience,
04/2016, Letnik:
10
Journal Article
Recenzirano
Odprti dostop
According to the traditional consolidation hypothesis which has dominated the literature concerning memory formation for more than 50 years, newly acquired information is progressively encoded into a ...stable long-term memory. In the same study, the authors demonstrated that inhibition of protein synthesis delivered within the brain also prevented enhanced dendritic spine density and synaptic strength normally observed in the engram cells engaged in the fear memory. ...either the morphological changes promoted by initial training were abolished by the post-reactivation PSI injection (which seems unlikely), or their difficulties in expressing fear arose from a source other than a lack of morphological changes.
Memory reactivation is an important process resulting from reexposure to salient training-related information whereby a memory is brought from an inactive to an active state. Reactivation is the ...first stage of memory retrieval but can result from the exposure to salient cues without any behavioral output. Such cue-induced reactivation, although frequently used by neuroscientists to study reconsolidation, has seldom been considered as a process in its own right and studied as such. This review presents arguments indicating that memory reactivation has two main consequences: (1) to enhance the accessibility of the target memory and (2) to make the memory malleable. Accordingly, reactivation creates a transient state during which the content of the memory is easily accessible and can be modified and/or updated. As both of these aspects can be observed shortly after memory reactivation, this review emphasizes that reconsolidation is not necessarily required for these processes and calls attention to reactivation as a factor in the dynamics of the memory.
Rats trained in a dual-solution cross-maze task, which can be solved by place and response strategies, predominantly used a response strategy after extensive training. This paper examines the ...involvement of the medial and lateral dorsal striatum (mDS and lDS) in the choice of these strategies after partial and extensive training. Our results show that rats with lDS and mDS lesions used mainly a response strategy from the early phase of training. We replicated these unexpected data in rats with lDS lesions and confirmed their tendency to use the response strategy in a modified cross-maze task. When trained in a dual-solution water-maze task, however, control and lesioned rats consistently used a place strategy, demonstrating that lDS and mDS lesioned rats can use a place strategy and that the shift towards a response strategy did not systematically result from extensive training. The present data did not show any clear dissociation between the mDS and lDS in dual solution tasks. They further indicate that the dorsal striatum seems to determine the strategies adopted in a particular context but cannot be considered as a neural support for the response memory system. Accordingly, the role of the lateral and medial part of the dorsal striatum in egocentric/response memory should be reconsidered.
Post-traumatic stress disorder (PTSD) and addiction to drugs of abuse are two common diseases, showing high comorbidity rates. This review presents a number of evidence showing similarities between ...these two pathologies, especially the hyper-responsiveness to environmental cues inducing a reactivation of the target memory leading either to re-experiencing (PTSD), or drug craving. Accordingly, PTSD and addiction to drug of abuse might by considered as memory pathologies, underlined by the same physiological process. We propose that these two pathologies rely on an uncoupling of the monoaminergic systems. According to this hypothesis, exposure to extreme conditions, either negative (trauma) or positive (drugs) induced a loss of the reciprocal control that one system usually exerts on the other monoaminergic system, resulting to an uncoupling between the noradrenergic and the serotonergic systems. Results obtained in our laboratory, using animal models of these pathologies, demonstrate that after a trauma, such as after repeated drug injections, rats developed both a behavioral sensitization (increases of the locomotion in response to a stimulation of the monoaminergic systems) and a pharmacological sensitization (increases of noradrenergic release within the prefrontal cortex). These results support our hypothesis and led us to propose new and innovative therapeutic approaches consisting either to induce a re-coupling of the monoaminergic systems, or to modify the pathological memories by using an emotional memory remodeling. Extremely encouraging results have already been obtained in rats and in humans, opening new and promising therapeutic avenues.
The involvement of the medial prefrontal cortex (mPFC), and more particularly the prelimbic and infralimbic cortices (PL-IL area), in spatial memory remains controversial. The present study ...investigates the effects of neurotoxic lesions restricted to the PL-IL area of the mPFC in rats trained in two different spatial tasks. In experiment 1, PL-IL lesioned rats showed normal acquisition of a delayed non-matching to position task. They were also able to plan their responses for a prospective strategy but were transiently disrupted when the initial delay was extended. In experiment 2, rats were trained to locate one baited box among 13 identical boxes distributed on a circular arena. Lesioned rats performed normally when trained from a single start position but were severely disrupted when four start positions were used. A probe trial showed this deficit was not due to failure to learn the goal location. The addition of a proximal cue signalling the goal box helped lesioned rats to directly open the goal box, but did not compensate for greater distances that they travelled to reach it. Results from both experiments indicate that the PL-IL area is directly involved neither in allocentric spatial representations nor prospective memory and is not specifically involved in working memory. This area seems more likely to be involved in both attentional processes and behavioural flexibility that may be important for processing information for working memory as well as for spatial memory.
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