Active Avoidance Conditioning Research Articles

Toxicological and hygienic assessment of modern thermo-insulating polymer materials during thermal exposure

Introduction. Polyethylene and synthetic foam caoutchouc are used for thermal insulation of communications, at temperatures not exceeding 90 °C and 105 °C, respectively. Data on how these materials will behave in the appropriate temperature conditions was not be found. 
 The purpose of the study was to conduct a toxicological and hygienic assessment of products made of polyethylene foam and synthetic foam rubber under thermal exposure.
 Materials and methods. The thermal effect on the studied samples was modelled in a climate chamber. The time interval during the mass loss of the samples was determined, a sanitary and chemical study of the gas-air mixture in the climatic chamber was carried out. To conduct a toxicological and hygienic study in animals, a swim-escape conditioned active avoidance response was developed.
 Results. Under thermal (90 °C) exposure for 72 hours to polyethylene tube, a loss of 0.77% of the initial mass of the sample occurs. Thermal exposure (105 °C) to synthetic foam caoutchouc resulted in a loss of 15.3% of the initial mass of the sample for 108 hours, while pronounced changes in the appearance of the samples were determined. When conducting a sanitary and chemical study in the climate chamber, an increase in the concentration of carbon monoxide was determined after 12, 24, and 72 hours and hydrogen chloride after 12 and 24 hours following the onset of thermal exposure compared with the values of their average daily maximum permissible concentration. Thermal exposure to the sample and synthetic foam caoutchouc led to an increase in the concentration of ammonia, carbon monoxide and hydrogen chloride 12 and 24 hours after the start of exposure compared with the average daily maximum permissible concentration. During the toxicological and hygienic study, animals exposed to thermal degradation products of the materials under study were revealed to show learning disabilities.
 Limitations. They are conditioned by the methodology of the study. A quantitative analysis of some gaseous thermal degradation products released into the climate chamber was performed, without taking into account the aerosols formed.
 Conclusion. Thermal insulation materials made of synthetic foam rubber and polyethylene foam lose their structural properties when they are operated in the maximum permissible temperature conditions (105 °C and 90 °C, respectively). When they are used in appropriate temperature conditions, the formation of toxic products occurs, the inhalation effect of which leads to a disturbances of the learning ability in laboratory animals.

Comparison of the effects of amitriptyline, melipramine and fluoxetine on acquisition and spatial alteration of avoidance responses in rats

The effects of amitriptyline (10 mg/kg), melipramine (10 mg/kg), and fluoxetine (5 mg/kg) on the acquisition of conditioned active avoidance responses and their spatial alteration in rats were studied. During the acquisition of avoidance, a passage in the partition was open, adjacent to the rear wall of the shuttle chamber. On the 5th experimental day after the end of the training, this distal opening was closed and the proximal one was opened, after which avoidance performance under changed conditions was tested for 20 trials. Melipramine and amitriptyline accelerated the acquisition of avoidance responses. Changing the location of the opening disrupted the learned skill, especially in the control animals. Melipramine and fluoxetine statistically significantly (in contrast to amitriptyline) accelerated the recovery of the level of avoidance. The positive effect of melipramine and fluoxetine is explained by a psychostimulating component in their spectrum. The inability of amitriptyline to produce a significant effect in this model is due to its psychosedative properties. The data obtained allow us to conclude that the acquisition of the active conditioned avoidance responses and their spatial modification can be used to analyze the antidepressant activity of pharmacological agents.

Sex-dependent deficits in associative learning across multiple LPS doses

Activation of the immune system by administration of the bacterial endotoxin lipopolysaccharide (LPS) impairs cognitive and neural plasticity processes. For instance, acute LPS exposure has been reported to impair memory consolidation, spatial learning and memory, and associative learning. However, the inclusion of both males and females in basic research is limited. Whether LPS-induced cognitive deficits are comparable in males and females is currently unclear. Therefore, the present study evaluated sex differences in associative learning following administration of LPS at a dose (i.e., 0.25 mg/kg) that impairs learning in males and higher LPS doses (i.e., 0.325 – 1 mg/kg) across multiple experiments. Adult male and female C57BL/6J mice were trained in a two-way active avoidance conditioning task following their respective treatments. Results showed that LPS had sex-dependent effects on associative learning. The 0.25 mg/kg LPS dose impaired learning in males, consistent with prior work. However, LPS, at any of the doses employed across three experiments, did not disrupt associative learning in females. Female mice were resistant to learning deficits despite showing heightened levels of select proinflammatory cytokines in response to LPS. Collectively, these findings demonstrate that the learning impairments resulting from acute LPS exposure are sex-dependent.

Cognitive function restoration in rats with chronic brain ischemia using Semax and hopantenic acid comprehensive administration

The relevance and importance of treating patients with ischemic brain lesions are indisputable. Chronic ischemic processes in the brain occur much more frequently than acute cerebral circulation disorders, leading to prolonged disability and being the main contributors to a significant number of strokes. Cognitive dysfunctions prevail in the dynamics of the post-ischemic period and are often the primary determinants of the severity of residual organic and subsequent functional impairments of the brain. The aim of the study is to investigate the effectiveness of separate and combined administration of Semax and hopantenic acid in the pharmacological correction of cognitive disorders in rats with experimental chronic brain ischemia. It has been established that rats with chronic brain ischemia exhibit cognitive impairments from the 1st day, manifested in worsened learning processes, short-term and long-term memory functioning in the context of conditioned active avoidance and conditioned feeding reflexes. It has been shown that separate and combined application of Semax and hopantenic acid contributes to the restoration of the learning process and improvement of mnestic functions in rats with chronic brain ischemia. The most pronounced nootropic effect in rats with chronic brain ischemia was registered under the conditions of combined administration of Semax and hopantenic acid, starting from the 3rd day of the study. Subsequently, in terms of anti-ischemic efficacy, the effect of Semax follows, which was realized starting from the 3rd day of the study. The least pronounced neuroprotective effect belongs to hopantenic acid, starting from the 7th day of the study. The author considers the obtained data as experimental groundwork for the feasibility of clinically testing the nootropic effects of the combined administration of Semax and hopantenic acid in cases of chronic brain ischemia. The comprehensive pharmacological correction of cognitive disorders in chronic brain ischemia is pathogenetically justified and aimed at activating sanogenetic mechanisms.

Involvement of Cerebellar Neural Circuits in Active Avoidance Conditioning in Zebrafish.

When animals repeatedly receive a combination of neutral conditional stimulus (CS) and aversive unconditional stimulus (US), they learn the relationship between CS and US, and show conditioned fear responses after CS. They show passive responses such as freezing or panic movements (classical or Pavlovian fear conditioning), or active behavioral responses to avoid aversive stimuli (active avoidance). Previous studies suggested the roles of the cerebellum in classical fear conditioning but it remains elusive whether the cerebellum is involved in active avoidance conditioning. In this study, we analyzed the roles of cerebellar neural circuits during active avoidance in adult zebrafish. When pairs of CS (light) and US (electric shock) were administered to wild-type zebrafish, about half of them displayed active avoidance. The expression of botulinum toxin, which inhibits the release of neurotransmitters, in cerebellar granule cells (GCs) or Purkinje cells (PCs) did not affect conditioning-independent swimming behaviors, but did inhibit active avoidance conditioning. Nitroreductase (NTR)-mediated ablation of PCs in adult zebrafish also impaired active avoidance. Furthermore, the inhibited transmission of GCs or PCs resulted in reduced fear-conditioned Pavlovian fear responses. Our findings suggest that the zebrafish cerebellum plays an active role in active avoidance conditioning.

Early Chronic Methamphetamine Exposure Induces Cognitive Impairments and Oxidative Damage in Adult Mice

Prescription stimulant misuse among young adults has gained popularity in the United States over the last decade, with amphetamine compounds becoming the second most common illicit drug used in college students. Misuse of these drugs can pose serious risks due to their high potential for abuse that can lead to dependency and neurotoxicity. Furthermore, there are prominent sex differences in psychostimulant use: men use more frequently and women have higher success rates in treatment but are more vulnerable to dependence and adverse effects. Psychostimulants, even at moderate doses, have been shown to promote oxidative stress, via auto-oxidation or metabolism of accumulated redox active dopamine. Oxidative stress has also been implicated in neurobehavioral impairments. Therefore, exposure to psychostimulants as a consequence of abuse would provide a second hit predicted to increase brain impairments. Moreover, the mesocorticolimbic pathway, a critical dopaminergic pathway, is particularly vulnerable to oxidative insults, and reveals sex-dependent differences in dopamine dynamics. We hypothesized that oxidative stress may act as a prominent cellular mechanism in mediating psychostimulant-induced neurotoxicity and neurobehavioral deficits. The purpose of this pilot study was to determine the short-term consequences of chronic, low toxic dosing of the prototypical psychostimulant, methamphetamine (METH), on cognition and markers of oxidative stress and dopaminergic function. Groups of young male and female (4-month-old) C57BL/6J mice received non-contingent intraperitoneal injections of either saline or methamphetamine (1.4 mg/kg) twice a day for 4 weeks. Two weeks following the last injection, animals were tested for cognitive function using 3 different tests: Morris water maze, active avoidance, and fear conditioning. After the completion of behavioral testing, brain regions were dissected and markers of oxidative stress and dopaminergic function were assayed. METH administration appeared to induce deficits in spatial learning and memory in both males and females, and in active avoidance and fear conditioning response in female mice only. Markers of dopaminergic function do not seem to be majorly affected by METH administration, while markers of lipid peroxidation were increased in the cortex and hippocampus of METH-treated females. These preliminary results suggest that chronic administration of METH induced impairments in cognitive function and changes in oxidative stress. These data indicate functional and biochemical changes that may have long-term consequences on brain function which will be the focus of future studies.

Stress-Induced Enhanced Long-Term Potentiation and Reduced Threshold for N-Methyl-D-Aspartate Receptor- and β-Adrenergic Receptor-Mediated Synaptic Plasticity in Rodent Ventral Subiculum.

Stress is a biologically relevant signal and can modulate hippocampal synaptic plasticity. The subiculum is the major output station of the hippocampus and serves as a critical hub in the stress response network. However, stress-associated synaptic plasticity in the ventral subiculum has not been adequately addressed. Therefore, we investigated the impact of a single exposure to an inherently stressful two-way active avoidance conditioning on the induction of long-term potentiation (LTP) at CA1—subiculum synapses in ventral hippocampal slices from young adult rats 1 day after stressor exposure. We found that acute stress enhanced LTP and lowered the induction threshold for a late-onset LTP at excitatory CA1 to subicular burst-spiking neuron synapses. This late-onset LTP was dependent on the activation of β-adrenergic and glutamatergic N-methyl-D-aspartate receptors and independent of D1/D5 dopamine receptor activation. Thereby, we present a cellular mechanism that might contribute to behavioral stress adaptation after acute stressor exposure.

The Peculiar Features of Cognitive Processes in Rats Exposed to a Hypomagnetic Field Using Moderate Magnetic Shielding

This paper is focused on the dynamics of the formation of conditioned responses in rats that experienced 14-day moderate magnetic shielding and were placed into a shelter setup when conducting the Barnes maze task. It was found that the acquisition rate of the conditioned active avoidance response was faster in rats under magnetic shielding conditions than that in the control animals. A direct accelerating effect of a moderate geomagnetic environment on the acquisition of the conditioned active avoidance response is thought to be extremely unlikely and the observed effect appears to be due to well-known biorhythm changes in pain sensitivity in hypomagnetic conditions associated with the development of hyperalgesia during the first week, which is an additional motivation for the formation of the conditioned active avoidance response in the Shelter setup. A two-phase change in pain sensitivity of male rats for a 14-day period was shown in the electrostimulation setup: hyperalgesia occurred during the first week and hypoalgesia was induced during the second week. The Barnes maze task did not reveal any differences between groups of control animals and experimental animals in recorded behavioral indices in hypomagnetic conditions within a 14-day period. Therefore, the accelerated formation of conditioned active avoidance response in rats under hypomagnetic conditions is most likely due to a significant increase in pain sensitivity during the first week of the experiment.

ALTERATIONS IN THE MRNA EXPRESSION OF D2 DOPAMINE RECEPTOR SPLICE VARIANTS AS POSSIBLE MECHANISM OF PREFRONTAL DYSFUNCTION AFTER EARLY-LIFE IMMUNE CHALLENGE

Various detrimental factors during early life may affect CNS development and increase risk of neuropsychiatric symptoms in later life. Disruption in brain dopaminergic system maturation is believed to be one of the mechanism of different neurodevelopmental disordrers. In this article we review behavioral peculiarities and changes of prefrontal D2 dopamine receptor splice variants (D2S and D2L) expression in rats after chronic experimental increase of proinflammatory cytokine interleukin(IL)-1β during 3rd week of life. Early life IL-1β treatment produce long lasting working memory deficit originating in juvenile adult animals. Elevation of IL-1β during 3rd week of life also affect developmental expression of D2 dopamine receptor mRNAs leading to increased D2S/D2L ratio in the medial prefrontal cortex of adolescent but not adult rats. Early life IL-1β treatment cancelled the learning-induced D2L mRNA downregulation during active avoidance conditioning in adult rats. Thus, dysregulation of expression of distinct D2 dopamine receptor splice variants within medial prefrontal cortex is supposed to be implicated in cognitive decline caused by early life immune challenge.

Behavior of Rats with High and Low Levels of Freezing in Defensive Situations and on Selection of Food Reinforcement

Behavior in rats with different levels of freezing in a classical defensive conditioned reflex was compared on acquisition of conditioned passive and active avoidance reflexes and on selection of food reinforcement of different values. Rats with prolonged freezing acquired the passive avoidance reflex better and retained it longer during extinction than animals with shorter freezing. At the same time, the active avoidance reflex in the shuttle box was acquired more easily by animals with short periods of freezing. Rats with prolonged freezing preferred a delayed and more valuable reinforcement in the model of choosing food reinforcements of different values (low level of impulsivity), while animals with short freezing preferred the low-value reinforcement without a delay (high level of impulsivity). The thresholds of pain sensitivity were no different in rats of the different groups. Thus, rats with prolonged freezing demonstrated a passive behavioral strategy in defensive situations and a low level of impulsivity, while rats with short freezing used an active behavioral strategy and showed a high level of impulsivity.

Rewarding deep brain stimulation at the medial forebrain bundle favours avoidance conditioned response in a remote memory test, hinders extinction and increases neurogenesis

Intracranial Self-Stimulation (ICSS) at the medial forebrain bundle consistently facilitates learning and memory in rats when administered post-training or when administered non-concurrent to training, but its scope regarding remote memory has not yet been studied. The present work aims to test whether the combination of these two forms of ICSS administration can cause a greater persistence of the facilitating effect on remote retention and affect neurogenesis in the dentate gyrus (DG) of the hippocampus.Rats were trained in active avoidance conditioning and tested in two retention sessions (10 and 90 days) and later extinction. Subjects received an ICSS session after each of the five avoidance acquisition sessions (post-training treatment) and half of them also received ten additional ICSS sessions during the rest period between retention tests (non-concurrent treatment). All the stimulated groups showed a higher performance in acquisition and retention sessions, but only the rats receiving both ICSS treatments showed greater resistance to extinction. Remarkably, at seven months, rats receiving the non-concurrent ICSS treatment had a greater number of DCX-positive cells in the DG as well as a higher amount of new-born cells within the granular layer compared to rats that did not receive this additional ICSS treatment.Our present findings significantly extend the temporal window of the facilitating effect of ICSS on active avoidance and demonstrate a neurogenic effect of rewarding medial forebrain bundle stimulation.

Aromatic Bromination Abolishes the Psychomotor Features and Pro-social Responses of MDMA ("Ecstasy") in Rats and Preserves Affinity for the Serotonin Transporter (SERT).

The entactogen MDMA (3,4-methylenedioxy-methamphetamine, “Ecstasy”) exerts its psychotropic effects acting primarily as a substrate of the serotonin transporter (SERT) to induce a non-exocytotic release of serotonin. Nevertheless, the roles of specific positions of the aromatic ring of MDMA associated with the modulation of typical entactogenic effects, using analogs derived from the MDMA template, are still not fully understood. Among many possibilities, aromatic halogenation of the phenylalkylamine moiety may favor distribution to the brain due to increased lipophilicity, and sometimes renders psychotropic substances of high affinity for their molecular targets and high potency in humans. In the present work, a new MDMA analog brominated at C(2) of the aromatic ring (2-Br-4,5-MDMA) has been synthesized and pharmacologically characterized in vitro and in vivo. First, binding competition experiments against the SERT-blocker citalopram were carried out in human platelets and compared with MDMA. Besides, its effects on platelet aggregation were performed in platelet enriched human plasma using collagen as aggregation inductor. Second, as platelets are considered an appropriate peripheral model for estimating central serotonin availability, the functional effects of 2-Br-4,5-MDMA and MDMA on ATP release during human platelet aggregation were evaluated. The results obtained showed that 2-Br-4,5-MDMA exhibits higher affinity for SERT than MDMA and fully abolishes both platelet aggregation and ATP release, resembling the pharmacological profile of citalopram. Subsequent in vivo evaluation in rats at three dose levels showed that 2-Br-4,5-MDMA lacks all key MDMA-like behavioral responses in rats, including hyperlocomotion, enhanced active avoidance conditioning responses and increased social interaction. Taken together, the results obtained are consistent with the notion that 2-Br-4,5-MDMA should not be expected to be an MDMA-like substrate of SERT, indicating that aromatic bromination at C(2) modulates the pharmacodynamic properties of the substrate MDMA, yielding a citalopram-like compound.

Microglia activation in the offspring of prenatal Poly I: C exposed rats: a PET imaging and immunohistochemistry study

BackgroundThe well-known ‘pyrotherapy’ of Julius Wagner-Jauregg might be the beginning of the study on the immunological concepts of schizophrenia. As the primary immune effector cells in the brain, microglia play...

Sleep deprivation impairs cognitive performance in zebrafish: A matter of fact?

The zebrafish (Danio rerio) has become a valuable model organism for behavioral studies examining learning and memory. Its diurnal circadian rhythm and characterized sleep-like state make it comparable to mammals, features that have contributed to establishing this small vertebrate as a translational model for sleep research. Despite sleep being an evolutionarily conserved behavior, its mechanisms and functions are still debated. Sleep deprivation is commonly associated with decreased attention, reduced responsiveness to external stimuli, altered locomotor activity and impaired performance on cognitive tasks. In the current study, we examined the effects of partial and total sleep deprivation on zebrafish learning performance in an active avoidance conditioning paradigm. In addition, we examined the effects of two drugs known to alter sleep (alcohol and melatonin) on learning performance in sleep deprived animals. Our results suggest that although partial sleep deprivation did not alter learning performance, total sleep deprivation was found to significantly impair behavioral responses to the electric shock as well as avoidance learning. However, when sleep deprived fish were treated with alcohol the night before the learning task, learning performance was similar to the control group. In contrast, melatonin treatment did not alter learning performance in sleep deprived animals. We conclude that the zebrafish is a sensitive tool for investigating the effects of sleep deprivation on cognitive performance and may be a useful model for dissecting the mechanisms underlying learning and memory.

Spaced sessions of avoidance extinction reduce spontaneous recovery and promote infralimbic cortex activation

Extinction-based therapies (EBT) are the psychological treatments of choice for certain anxiety disorders, such as post-traumatic stress disorder. However, some patients relapse and suffer spontaneous recovery (SR) of anxiety symptoms and persistence of avoidance behaviour, which underlines the need for improving EBT. In rats, recent evidence has highlighted the relevance of the temporal distribution of extinction sessions in reducing SR of auditory fear conditioning, although it has seldom been studied in procedures involving proactive avoidance responses, such as two-way active avoidance conditioning (TWAA).We examined whether the temporal distribution of two extinction sessions separated by 24h or 7days (contiguous versus spaced extinction paradigms, respectively), influences SR after 28days of a TWAA task. c-Fos expression, as a marker of neuronal activation, was also measured by immunohistochemistry 90min after the SR test in the amygdala and the medial prefrontal cortex.The temporal distribution of extinction sessions did not affect the degree of extinction learning. However, only the rats that underwent the 7-day spaced extinction paradigm maintained the level of extinction in the long term, showing no SR in TWAA. This behavioural finding was consistent with a greater number of c-Fos-labelled neurons in the infralimbic cortex in the 7-day group, and in the Lateral and Central nuclei of the amygdala in the 24-hour group. These findings show that a time-spaced extinction paradigm reduces the spontaneous recovery of active avoidance behaviour, and that this behavioural advantage appears to be related to the activation of the infralimbic cortex.

Genetically Induced Retrograde Amnesia of Associative Memories After Neuroplastin Ablation

Neuroplastin cell recognition molecules have been implicated in synaptic plasticity. Polymorphisms in the regulatory region of the human neuroplastin gene (NPTN) are correlated with cortical thickness and intellectual abilities in adolescents and in individuals with schizophrenia. We characterized behavioral and functional changes in inducible conditional neuroplastin-deficient mice. We demonstrate that neuroplastins are required for associative learning in conditioning paradigms, e.g., two-way active avoidance and fear conditioning. Retrograde amnesia of learned associative memories is elicited by inducible neuron-specific ablation of Nptn gene expression in adult mice, which shows that neuroplastins are indispensable for the availability of previously acquired associative memories. Using single-photon emission computed tomography imaging in awake mice, we identified brain structures activated during memory recall. Constitutive neuroplastin deficiency or Nptn gene ablation in adult mice causes substantial electrophysiologic deficits such as reduced long-term potentiation. In addition, neuroplastin-deficient mice reveal profound physiologic and behavioral deficits, some of which are related to depression and schizophrenia, which illustrate neuroplastin's essential functions. Neuroplastins are essential for learning and memory. Retrograde amnesia after an associative learning task can be induced by ablation of the neuroplastin gene. The inducible neuroplastin-deficient mouse model provides a new and unique means to analyze the molecular and cellular mechanisms underlying retrograde amnesia and memory.

Expression of the FGF2 and TIMP1 Genes in the Adult Rat Brain after Administration of Interleukin-1β during Early Postnatal Ontogeny

Hypotheses relating to the developmental nature of cognitive impairments in schizophrenia and other neuropathologies propose that the development of stable cognitive deficit involves important roles for hypoxia, trauma, and infections operating during the prenatal and early postnatal periods. These pathological states are accompanied by increases in the production of proinflammatory cytokine interleukin-1β (IL-1β) in cells of the nervous and immune systems. We report here studies of the characteristics of the expression of the Fgf1 and Timp1 genes, which are involved in regulating the cerebral mechanisms of neuroplasticity, in cells of the medial prefrontal cortex and the dorsal and ventral areas of the hippocampus in adult rats given IL-1β during early postnatal ontogeny. Experiments were performed in standard conditions and on acquisition of a conditioned active avoidance reflex. Learning impairments in experimental animals were accompanied by decreased production of FGF-2 mRNA in cells of the medial prefrontal cortex and ventral hippocampus. There were no differences between groups in conditions without cognitive loading.

Increase in c-Fos and Arc protein in retrosplenial cortex after memory-improving lateral hypothalamic electrical stimulation treatment

Post-training Intracranial self-stimulation (ICSS) of the lateral hypothalamus (LH), a kind of rewarding deep-brain stimulation, potentiates learning and memory and increases c-Fos protein expression in specific memory-related brain regions. In a previous study, Aldavert-Vera et al. (2013) reported that post-acquisition LH-ICSS improved 48h retention of a delay two-way active avoidance conditioning (TWAA) and induced c-Fos expression increase in CA3 at 90min after administration. Nevertheless, this c-Fos induction was only observed after the acquisition session and not after the retention test at 48h, when the ICSS improving effect was observed on memory. This current study aims to examine the hypothesis that post-training ICSS treatment may stimulate c-Fos expression at the time of the TWAA retention test in retrosplenial cortex (RSC), a hippocampus-related brain region more closely related with long-lasting memory storage. Effects of ICSS on Arc protein, a marker of memory-associated synaptic plasticity, were also measured by immunohistochemistry in granular and agranular RSC. The most innovative results are that the ICSS treatment potentiates the c-Fos induction across TWAA conditions (no conditioning, acquisition and retention), specifically in layer V of the granular RSC, along with increases of Arc protein levels in the granular but not in agranular areas of RSC ipsilaterally few hours after ICSS. This leads us to suggest that plasticity-related protein activation in the granular RSC could be involved in the positive modulatory effects of ICSS on TWAA memory consolidation, opening a new approach for future research in ICSS memory facilitation.

Differential effects of bupropion on acquisition and performance of an active avoidance task in male mice

Bupropion is an antidepressant drug that is known to aid smoking cessation, although little experimental evidence exists about its actions on active avoidance learning tasks. Our aim was to evaluate the effects of this drug on two-way active avoidance conditioning. In this study, NMRI mice received bupropion (10, 20 and 40mg/kg) or saline before a daily training session (learning phase, days 1–4) in the active avoidance task. Performance was evaluated on the fifth day (retention phase): in each bupropion-treated group half of the mice continued with the same dose of bupropion, and the other half received saline. Among the vehicle-treated mice, different sub-groups were challenged with different doses of bupropion. Results indicated that mice treated with 10 and 20mg/kg bupropion exhibited more number of avoidances during acquisition. The response latency confirmed this learning improvement, since this parameter decreased after bupropion administration. No differences between groups were observed in the retention phase. In conclusion, our data show that bupropion influences the learning process during active avoidance conditioning, suggesting that this drug can improve the control of emotional responses.

Trans-generational transmission of neurobehavioral impairments produced by developmental methylmercury exposure in zebrafish (Danio rerio)

Our previous study showed that embryonic exposures to methylmercury (MeHg) produced learning impairments in adult zebrafish. The present study investigated the persistency of learning impairments in the second (F2) and third (F3) generations of zebrafish developmentally exposed to MeHg as embryos using active avoidance conditioning as the behavioral paradigm. The results showed that the control zebrafish learned avoidance responses during training and significantly increased avoidance responses during testing. The F2 generation of zebrafish developmentally exposed to MeHg as embryos displayed no significant changes in avoidance responses from training to testing, showing persistent learning impairments, while the F3 generation of zebrafish developmentally exposed as embryos to only the higher concentration of MeHg showed persistent learning impairments. Results of the present study showed that learning impairments produced by embryonic MeHg exposure persisted for at least three generations, demonstrating trans-generational effects of embryonic exposure to MeHg.