Active Avoidance Response Research Articles

Ventral hippocampus inactivation enhances the extinction of active avoidance responses in the presence of safety signals but leaves discrete trial operant active avoidance performance intact.

The acquisition of active avoidance (AA) behavior is typically aided by the presence of two signals-the warning signal, which predicts the future occurrence of an aversive event (e.g., shocks), and the safety signal, which is presented upon successful avoidance of oncoming shocks. While the warning signal could be conceived to act as a Pavlovian fear cue, and is likely mediated by brain areas that underlie Pavlovian fear cue conditioning, the neural substrates underlying safety signaling are less clear, largely due to the unavailability of AA tasks that are devoid of an explicit warning signal. The present study sought to investigate the role of the ventral hippocampus (VH) in safety signaled AA performance acquired without an explicit warning signal, using a novel discrete trial paradigm. Adult male Long Evans rats were divided into two groups and trained to acquire AA responses with, or without a safety signal. Analysis of the acquisition and stable state performance data revealed that the availability of a safety signal alone did not improve the acquisition or performance of AA responses. Furthermore, post-training, reversible VH inactivation did not impact stable state avoidance behavior. However, extinction of avoidance responses was facilitated in the group trained with a safety signal, and this effect was further potentiated by VH inactivation. Additional elevated plus maze (EPM), light-dark box, and locomotor tests demonstrated that VH inactivation reduced anxiety without affecting locomotor activity. Taken together, these results demonstrate the importance of VH in the extinction of persistent pathological avoidance behavior when safety is signaled.

Effects of resveratrol and soy isoflavones on learning and memory ability and expression of glucose transporter in aging model rats

To investigate the effects of resveratrol combined with soy isoflavones on avoidance memory, number of neuron-specific nuclear protein(NeuN) positive cells and expressions of glucose transporter(GLUT)1 and GLUT3 in hippocampus of aging model rats. A total of 60 female SD rats were randomly divided into 6 groups including sham control group, aging model group, 80 mg/kg resveratrol group, 160 mg/kg soy isoflavones group, 80 mg/kg resveratrol +160 mg/kg soy isoflavones group, 0. 8 mg/kg estradiol valerate group. The aging model rats was induced by ovariectomy combined with intraperitoneal injection of 100 mg/kg D-galactose. Intragastric administration was performed once a day for 12 weeks. The avoidance task was measured by the shuttle box test. The NeuN expression were measured by the immunofluorescence. The genes and proteins expression of GLUT1 and GLUT3 in rat hippocampus were detected by real-time PCR and Western blot, respectively. Compared with the sham control group, the avoidance latency in the aging model group was prolonged, and the active avoidance response rate and the total avoidance response rate were decreased. The number of NeuN positive cells decreased and the expression levels of GLUT1 and GLUT3 genes and proteins were decreased(P<0. 05). Compared with the aging model group, the escape latency significantly declined(P<0. 01), but the rates of active avoidance response and total avoidance response increased, the number of NeuN positive cells increased significantly, the expression levels of GLUT1 and GLUT3 genes and proteins up-regulated in the rats of the three intervention groups(P<0. 05 or P<0. 01). Compared with the soy isoflavones group, the active avoidance response rate was increased in the combined group(P<0. 05). In comparison with those for the resveratrol group, the avoidance latency was shortened and the active avoidance response rate was increased, the number of NeuN positive cells and the expression levels of GLUT3 gene and protein were significantly increased in the combined group(P<0. 05). There was no significant difference between the combined intervention group and the estradiol valerate group(P>0. 05). Resveratrol and soy isoflavones alone and in combination can improve the learning and memory ability of aging rat models. The mechanism may be related to up-regulating the expression of GLUT1 and GLUT3 genes and proteins in the hippocampus, promoting the transmembrane transport of glucose and reducing neuronal loss.

LW-AFC, a new formula from the traditional Chinese medicine Liuwei Dihuang decoction, as a promising therapy for Alzheimer's disease: Pharmacological effects and mechanisms.

LW-AFC is a new formula derived from the Liuwei Dihuang decoction, a classical traditional Chinese medicine prescription. Based on our research, LW-AFC is a promising drug for Alzheimer's disease (AD). The studies were conducted primarily in two typical AD mouse models: SAMP8 and APP/PS1 mice. The results showed that LW-AFC could improve many cognitive behaviors, such as spatial learning and memory ability, passive and active avoidance response, and object recognition memory capability. In addition, LW-AFC could also alleviate the AD-like pathology in animal models, such as neuron loss and Aβ deposition. Subsequent studies found that LW-AFC could rebalance hypothalamic-pituitary-adrenal (HPA) axis and hypothalamic-pituitary-gonadal (HPG) axis, and modulate the disturbance of immune system and gut flora. These data suggested that the anti-AD effects of LW-AFC might be mainly via modulating the neuroendocrine immunomodulation (NIM) network. As inhibiting the immune function by immunosuppressant could abolish the protective effects of LW-AFC against long-term potentiation (LTP) impairment model, it is likely that LW-AFC balancing the NIM network is initiated by modulating the immune system.

Zona Incerta GABAergic Output Controls a Signaled Locomotor Action in the Midbrain Tegmentum.

The zona incerta is a subthalamic nucleus proposed to link sensory stimuli with motor responses to guide behavior, but its functional role is not well established. Using mice of either sex, we studied the effect of manipulating zona incerta GABAergic cells on the expression of a signaled locomotor action, known as signaled active avoidance. We found that modulation of GABAergic zona incerta cells, but not of cells in the adjacent thalamic reticular nucleus (NRT), fully controls the expression of signaled active avoidance responses. Inhibition of zona incerta GABAergic cells drives active avoidance responses, while excitation of these cells blocks signaled active avoidance mainly by inhibiting cells in the midbrain pedunculopontine tegmental nucleus (PPT). The zona incerta regulates signaled locomotion in the midbrain.

Circuits That Mediate Expression of Signaled Active Avoidance Converge in the Pedunculopontine Tegmentum.

An innocuous sensory stimulus that reliably signals an upcoming aversive event can be conditioned to elicit locomotion to a safe location before the aversive outcome ensues. The neural circuits that mediate the expression of this signaled locomotor action, known as signaled active avoidance, have not been identified. While exploring sensorimotor midbrain circuits in mice of either sex, we found that excitation of GABAergic cells in the substantia nigra pars reticulata blocks signaled active avoidance by inhibiting cells in the pedunculopontine tegmental nucleus (PPT), not by inhibiting cells in the superior colliculus or thalamus. Direct inhibition of putative-glutamatergic PPT cells, excitation of GABAergic PPT cells, or excitation of GABAergic afferents in PPT, abolish signaled active avoidance. Conversely, excitation of putative-glutamatergic PPT cells, or inhibition of GABAergic PPT cells, can be tuned to drive avoidance responses. The PPT is an essential junction for the expression of signaled active avoidance gated by nigral and other synaptic afferents.SIGNIFICANCE STATEMENT When a harmful situation is signaled by a sensory stimulus (e.g., street light), subjects typically learn to respond with active or passive avoidance responses that circumvent the threat. During signaled active avoidance behavior, subjects move away to avoid a threat signaled by a preceding innocuous stimulus. We identified a part of the midbrain essential to process the signal and avoid the threat. Inhibition of neurons in this area eliminates avoidance responses to the signal but preserves escape responses caused by presentation of the threat. The results highlight an essential part of the neural circuits that mediate signaled active avoidance behavior.

A combination of indomethacin and atorvastatin ameliorates cognitive and pathological deterioration in PrP-hAβPPswe/PS1ΔE9 transgenic mice

Mounting evidence has shown that inflammation might drive Alzheimer's disease (AD) pathology and contribute to its exacerbation. Previous studies have indicated that indomethacin or atorvastatin are beneficial in treating AD; however, no significant clinical effects have been shown. Furthermore, no study has investigated the efficacy of combining these agents for treating AD. This study sought to determine the effect of a combination of indomethacin and atorvastatin in the PrP-hAβPPswe/PS1ΔE9 (APP/PS1) transgenic AD mouse model. Treatment with indomethacin and atorvastatin ameliorated impairments in spatial learning and memory, and the active avoidance response in APP/PS1 mice. Moreover, we found a suppression of Aβ plaques and decreased concentration of Aβ1–42 in the hippocampus of APP/PS1 mice following treatment. In addition, indomethacin and atorvastatin ameliorated abnormal cytokine secretion, lymphocyte subset disorder, and hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axis imbalances in APP/PS1 mice. The combination of indomethacin and atorvastatin restored immune and neuroendocrine processes, attenuated pathologic changes and cognitive impairments in APP/PS1 transgenic mice, and could thus be a potential therapeutic agent for AD.

Nrf2 deletion results in impaired performance in memory tasks and hyperactivity in mature and aged mice

Oxidative stress has been implicated in both the functional and cognitive decline associated with neuropsychiatric diseases and aging. A master regulator of the body's defense mechanism against oxidative stress is nuclear factor erythroid 2-related factor (NRF2). Here we investigated the effects of NRF2 deletion on motor and cognitive performance in “Aged” mice (17–25 months old) as compared to “Mature” mice (3–15 months old). We observed that the Aged Nrf2−/− mice were hyperactive and exhibited impaired acquisition of an active avoidance response. Furthermore, the Mature mice also displayed a hyperactive phenotype and had impaired working memory in the probe trial of the water radial arm maze. Overall, it appears that NRF2 may be implicated in memory and activity functions and its deletion exacerbates deficits associated with aging. These observations provide a model for assessing the role of oxidative stress in age-related disorders.

Stimulation of the Nigrotectal Pathway at the Level of the Superior Colliculus Reduces Threat Recognition and Causes a Shift From Avoidance to Approach Behavior.

Defensive behavioral responses are essential for survival in threating situations. The superior colliculus (SC) has been implicated in the generation of defensive behaviors elicited by visual, tactile and auditory stimuli. Furthermore, substantia nigra pars reticulata (SNr) neurons are known to exert a modulatory effect on midbrain tectum neural substrates. However, the functional role of this nigrotectal pathway in threating situations is still poorly understood. Using optogenetics in freely behaving mice, we activated SNr projections at the level of the SC, and assessed consequences on behavioral performance in an open field test (OFT) and the beetle mania task (BMT). The latter confronts a mouse with an erratic moving robo-beetle and allows to measure active and passive defensive responses upon frequent encounter of the threatening object. Channelrhodopsin-2 (ChR2)-mediated activation of the inhibitory nigrotectal pathway did not affect anxiety-like and exploratory behavior in the OFT, but increased the number of contacts between robo-beetle and test mouse in the BMT. Depending on the size of the arena, active avoidance responses were reduced, whereas tolerance and close following of the robo-beetle were significantly increased. We conclude from the data that the nigrotectal pathway plays holds the potential to modulate innate fear by attenuating threat recognition and causing a shift from defensive to approach behavior.

Expression of BDNF and trkB in the hippocampus of a rat genetic model of vulnerability (Roman low-avoidance) and resistance (Roman high-avoidance) to stress-induced depression.

IntroductionThe selective breeding of Roman High‐ (RHA) and Low‐Avoidance (RLA) rats for, respectively, rapid versus poor acquisition of the active avoidance response has generated two distinct phenotypes differing in many behavioral traits, including coping strategies to aversive conditions. Thus, RLA rats are considered as a genetic model of vulnerability to stress‐induced depression whereas RHA rats are a model of resilience to that trait. Besides the monoamine hypothesis of depression, there is evidence that alterations in neuronal plasticity in the hippocampus and other brain areas are critically involved in the pathophysiology of mood disorders.Materials and MethodsWestern blot (WB) and immunohistochemistry were used to investigate the basal immunochemical occurrence of brain‐derived neurotrophic factor (BDNF) and its high‐affinity tyrosine‐kinase receptor trkB in the dorsal and ventral hippocampus of adult RHA and RLA rats.Results WB analysis indicated that the optical density of BDNF‐ and trkB‐positive bands in the dorsal hippocampus is, respectively, 48% and 25% lower in RLA versus RHA rats. Densitometric analysis of BDNF‐ and trkB‐like immunoreactivity (LI) in brain sections showed that BDNF‐LI is 24% to 34% lower in the different sectors of the Ammon's horn of RLA versus RHA rats, whereas line‐related differences are observed in the dentate gyrus (DG) only in the ventral hippocampus. As for trkB‐LI, significant differences are observed only in the dorsal hippocampus, where density is 23% lower in the DG of RLA versus RHA rats, while no differences across lines occur in the Ammon's horn.ConclusionThese findings support the hypothesis that a reduced BDNF/trkB signaling in the hippocampus of RLA versus RHA rats may contribute to their more pronounced vulnerability to stress‐induced depression.

Infant avoidance training alters cellular activation patterns in prefronto-limbic circuits during adult avoidance learning: II. Cellular imaging of neurons expressing the activity-regulated cytoskeleton-associated protein (Arc/Arg3.1).

Positive and negative feedback learning is essential to optimize behavioral performance. We used the two-way active avoidance (TWA) task as an experimental paradigm for negative feedback learning with the aim to test the hypothesis that neuronal ensembles activate the activity-regulated cytoskeletal (Arc/Arg3.1) protein during different phases of avoidance learning and during retrieval. A variety of studies in humans and other animals revealed that the ability of aversive feedback learning emerges postnatally. Our previous findings demonstrated that rats, which as infants are not capable to learn an active avoidance strategy, show improved avoidance learning as adults. Based on these findings, we further tested the hypothesis that specific neuronal ensembles are "tagged" during infant TWA training and then reactivated during adult re-exposure to the same learning task. Using cellular imaging by immunocytochemical detection of Arc/Arg3.1, we observed that, compared to the untrained control group, (1) only in the dentate gyrus the density of Arc/Arg3.1-expressing neurons was elevated during the acquisition phase of TWA learning, and (2) this increase in Arc/Arg3.1-expressing neurons was not specific for the TWA learning task. With respect to the effects of infant TWA training we found that compared to the naïve non-pretrained group (a) the infant pretraining group displayed a higher density of Arc/Arg3.1-expressing neurons in the anterior cingulate cortex during acquisition on training day 1, and (b) the infant pretraining group displayed elevated density of Arc/Arg3.1-expressing neurons in the dentate gyrus during retrieval on test day 5. Correlation analysis for the acquisition phase revealed for the ACd that the animals which showed the highest number of avoidances and the fastest escape latencies displayed the highest density of Arc/Arg3.1-expressing neurons. Taken together, we are the first to use the synaptic plasticity protein Arc/Arg3.1 to label neuronal ensembles which are involved in different phases of active avoidance learning and whose activity patterns are changing in response to previous learning experience during infancy. Our results indicate (1) that, despite the inability to learn an active avoidance response in infancy, lasting memory traces are formed encoding the subtasks that are learned in infancy (e.g., the association of the CS and UCS, escape strategy), which are encoded in the infant brain by neuronal ensembles, which alter their synaptic connectivity via activation of specific synaptic plasticity proteins such as Arc/Arg3.1 and Egr1, and (2) that during adult training these memories can be retrieved by reactivating these neuronal ensembles and their synaptic circuits and thereby accelerate learning.

Dopamine, Noradrenaline and Differences in Sexual Behavior between Roman High and Low Avoidance Male Rats: A Microdialysis Study in the Medial Prefrontal Cortex.

Roman High- (RHA) and Low-Avoidance (RLA) outbred rats, which differ for a respectively rapid vs. poor acquisition of the active avoidance response in the shuttle-box, display differences in sexual activity when put in the presence of a sexually receptive female rat. Indeed RHA rats show higher levels of sexual motivation and copulatory performance than RLA rats, which persist also after repeated sexual activity. These differences have been correlated to a higher tone of the mesolimbic dopaminergic system of RHA rats vs. RLA rats, revealed by the higher increase of dopamine found in the dialysate obtained from the nucleus accumbens of RHA than RLA rats during sexual activity. This work shows that extracellular dopamine and noradrenaline (NA) also, increase in the dialysate from the medial prefrontal cortex (mPFC) of male RHA and RLA rats put in the presence of an inaccessible female rat and more markedly during direct sexual interaction. Such increases in dopamine (and its main metabolite 3,4-dihydroxyphenylacetic acid, DOPAC) and NA were found in both sexually naïve and experienced animals, but they were higher: (i) in RHA than in RLA rats; and (ii) in sexually experienced RHA and RLA rats than in their naïve counterparts. Finally, the differences in dopamine and NA in the mPFC occurred concomitantly to those in sexual activity, as RHA rats displayed higher levels of sexual motivation and copulatory performance than RLA rats in both the sexually naïve and experienced conditions. These results suggest that a higher dopaminergic tone also occurs in the mPFC, together with an increased noradrenergic tone, which may be involved in the different copulatory patterns found in RHA and RLA rats, as suggested for the mesolimbic dopaminergic system.

High risk no gain-metabolic performance of hatchery reared Atlantic salmon smolts, effects of nest emergence time, hypoxia avoidance behaviour and size

When animals are reared for conservational releases it is paramount to avoid reducing genetic and phenotypic variation over time. This requires an understanding of how diverging behavioural and physiological traits affect performance both in captivity and after release. In Atlantic salmon, emergence time from the spawning gravel has been linked to certain behavioural and physiological characteristics and to the concept of stress coping styles. Early emerging fry has for example been shown to be bolder and more aggressive and to have higher standard metabolic rates compared to late emerging fry. The first aim was therefore to examine if emergence latency affect the behavioural stress coping response also beyond the fry and parr stage. This was done using a hypoxia avoidance test, where an active behavioural avoidance response can be related to higher risk taking. No behavioural differences were found between the two emergence fractions either at the parr or pre-smolt stage, instead smaller individuals were more prone to express an “active” hypoxia avoidance response. Further, an individual expressing a “passive” response as parr were also more prone to express this behaviour at the pre-smolt stage. While there are some previous studies showing that early emerging individuals with a bolder personality may be favored within a hatchery setting it is not known to what extent these early differences persist to affect performance after release. The second aim was therefore to compare the physiological performance at the time of release as smolts using the two subgroups; 1) early emerging fish showing active hypoxia avoidance (Early+Bold) and 2) late emerging fish showing a passive hypoxia response (Late+Shy). The Early+Bold group showed a higher red blood cell swelling, suggesting a higher adrenergic output during stress, whereas there was no difference in post-stress plasma cortisol or physiological smolt status. While there was no difference in standard metabolic rate between the groups, the Early+Bold group exhibited a lower maximum metabolic rate and aerobic scope following strenuous swimming. In captivity this may have no clear negative effects, but in the wild, a more risk prone behavioural profile linked to a lower aerobic capacity to escape from e.g. a predator attack, could clearly be disadvantageous.

The effect of ingested sulfite on active avoidance in normal and sulfite oxidase-deficient aged rats

The aim of this study was to investigate the possible toxic effects of sulfite on neurons by measuring active avoidance learning in normal and sulfite oxidase (SOX)-deficient aged rats. Twenty-four months of age Wistar rats were divided into four groups: control (C), sulfite-treated group (S), SOX-deficient group (D) and SOX-deficient + sulfite-treated group (DS). SOX deficiency was established by feeding rats with a low molybdenum (Mo) diet and adding 200 ppm tungsten (W) to their drinking water. Sulfite in the form of sodium metabisulfite (25 mg/kg) was given by gavage for six weeks. Active avoidance responses were determined by using an automated shuttle box. Hepatic SOX activity was measured to confirm SOX deficiency. The hippocampus was used for determining the activity of cyclooxygenase (COX) and caspase-3 enzymes and the level of prostaglandin E2 (PGE2) and nitrate/nitrite. SOX-deficient rats had an approximately 10-fold decrease in hepatic SOX activity compared with normal rats. Sulfite did not induce impairment of active avoidance learning in SOX-deficient rats and in normal rats compared with their control groups. Sulfite had no effect on the activity of COX and caspase-3 in the hippocampus. Treatment with sulfite did not significantly increase the level of PGE2 and nitrate/nitrite in the hippocampus.

The Effects of LW-AFC on Intestinal Microbiome in Senescence-Accelerated Mouse Prone 8 Strain, a Mouse Model of Alzheimer's Disease.

Microbes have deserved broader attention as causal factors in Alzheimer's disease (AD), a neurodegenerative disorder. The senescence-accelerated mouse prone 8 (SAMP8) strain, a spontaneous mice of accelerated aging, are considered a robust model for sporadic AD. LW-AFC, an herbal medicine, was prepared from LiuweiDihuang decoction, which is a classical traditional Chinese medicine prescription. Here, we showed that the treatment of LW-AFC improved cognitive impairments of SAMP8 mice, including spatial learning and memory ability, active avoidance response, and object recognition memory capability. Our data indicated that there were significantly 8 increased and 12 decreased operational taxonomic units (OTUs) in the gut microbiota of SAMP8 mice compared with senescence accelerated mouse resistant 1 (SAMR1) strains, the control of SAMP8 mice. The treatment of LW-AFC altered 22 (16 increased and 6 decreased) OTUs in SAMP8 mice and among them, 15 OTUs could be reversed by LW-AFC treatment resulting in a microbial composition similar to that of SAMR1 mice. We further showed that there were 7 (3 negative and 4 positive correlation) OTUs significantly correlated with all the three types of cognitive abilities, at the order level, including Bacteroidales, Clostridiales, Desulfovibrionales, CW040, and two unclassified orders. LW-AFC had influences on bacterial taxa correlated with the abilities of learning and memory in SAMP8 mice and restored them to SAMR1 mice. Our results indicate that the effects of LW-AFC on improving cognitive impairments of SAMP8 mice might be via modulating intestinal microbiome and LW-AFC could be used as a potential anti-AD agent.

Association between prepulse inhibition of the startle response and latent inhibition of two-way avoidance acquisition: A study with heterogeneous NIH-HS rats

This study presents the first evaluation of the associations between responses in two paradigms related to schizophrenia in the genetically heterogeneous NIH-HS rat stock. NIH-HS rats are a stock of genetically heterogeneous animals that have been derived from eight different inbred strains. A rotational breeding schedule has been followed for more than eighty generations, leading to a high level of genetic recombination that makes the NIH-HS rats a unique tool for studying the genetic basis of (biological, behavioral, disease-related) complex traits. Previous work has dealt with the characterization of coping styles, cognitive and anxiety/fear-related profiles of NIH-HS rats. In the present study we have completed their characterization in two behavioral models, prepulse inhibition (PPI) and latent inhibition (LI) of the two-way active avoidance response, that appear to be related to schizophrenia or to schizophrenia-relevant symptoms. We have found that these rats display PPI for each of the four prepulse intensities tested, allowing their stratification in high, medium and low PPI subgroups. When testing these three subgroups for LI of two-way active avoidance acquisition it has been observed that the LowPPI and MediumPPI subgroups present impaired LI, which, along with the fact that the HighPPI group presents significant LI, allows us to hypothesize that responses in these two paradigms are somehow related and that selection of NIH-HS rats for Low vs HighPPI could make a promising animal model for the study of clusters of schizophrenia-relevant symptoms and their underlying neurobiological mechanisms.

Differences in Active Avoidance Conditioning in Male and Female Rats with Experimental Anxiety-Depressive Disorder.

Using rat model of experimental anxiety-depressive disorder caused by postnatal administration of methionyl-2(S)-cyanopyrrolidine, an inhibitor of dipeptidyl peptidase IV, we compared conditioned active avoidance response and memory retention in males and females. In experimental males and females, conditioning was impaired in comparison with the control. In experimental groups, females were worse learners than males, while in control groups, females were better learners than males. Memory retention in experimental animals did not differ from that in controls 24 h after learning. Two months after learning, control females demonstrated better retention than control males.

Stress-protective effect of thymic peptides.

Experiments on Wistar rats showed that thymic peptides produce a stress-protective effect that manifested in prevention of functional impairment of conditioned active avoidance response and a decrease in generalized motor activity typical of higher nervous activity failure. We concluded that thymic peptides significantly modulate integrative functions of the brain and produce a stress-protective effect.

The effect of transcranial electromagnetic brain stimulation on the acquisition of the conditioned response in rats

We studied the effect of transcranial electromagnetic stimulation on the acquisition of the active avoidance response with pain reinforcement in laboratory rats. We demonstrate that in male rats exposure of the brain to electromagnetic irradiation in the millimeter range with λ = 5.6 or 7.1 mm, modulated by a series of low-frequency pulses, prevented the acquisition of the conditioned avoidance response to a pain stimulus in 50% of the animals. The irradiation inhibited avoidance conditioning in an additional 25% of the animals. Similar treatment with transcranial electromagnetic stimulation after intraperitoneal injection of the antagonist of serotonergic receptors kytril did not influence avoidance conditioning. The electromagnetic brain stimulation did not affect the maintenance of the conditioned response in the animals that had developed it previously. Based on these data we hypothesize that the transcranial electromagnetic stimulation that was used in the present study promotes the synthesis of serotonin, which inhibits the formation of temporary connections during avoidance conditioning.

Involvement of dopamine in the differences in sexual behaviour between Roman high and low avoidance rats: An intracerebral microdialysis study

Outbred Roman high- (RHA) and low-avoidance (RLA) rats are selected for respectively rapid vs. poor acquisition of the active avoidance response and display different copulatory patterns when exposed to a sexually receptive female, with RHA rats showing more robust sexual motivation and better performance than RLA rats also after repeated sexual activity. Here we show that the distinct patterns of sexual behaviour of the Roman lines are correlated with differences in the activity of the dopaminergic mesolimbic system, which plays a key role in sexual motivation and copulatory performance. Thus, differential increases in the concentrations of dopamine and its main metabolite 3,4-dihydroxyphenylacetic acid, occurred in dialysates obtained from the nucleus accumbens shell of naïve and sexually experienced Roman rats during the anticipatory and consummatory phases of sexual activity. These differences were particularly evident between sexually naïve RHA and RLA rats and tended to diminish but still persisted between sexually experienced rats, as did the differences in sexual behaviour. Analysis of the biochemical and behavioural findings showed that, while in RHA rats sexual experience caused a shift in the changes in both the dopaminergic activity and copulation towards the first period of the sexual test, in RLA rats sexual experience increased dopaminergic activity and copulation throughout the entire test. Therefore, this study adds experimental support to the view that the different sexual patterns of the Roman lines are due, at least in part, to a more robust functional tone of the mesolimbic dopaminergic system of RHA rats.

Carnosine (β-alanyl-L-histidine) increases the efficacy of learning under conditions of oxidative stress related to the development of conditioned response with negative reinforcement

Previously, using in vivo models hystidine containing dipeptide carnosine (β-alanyl-L-hystidine) was shown to inhibit the development of oxidative stress induced by such effects like hypoxia, ischemia and neurotoxin administration. These studies showed that animals having undergone oxidative stress in the settings of carnosine administration preserve habits developed in open field, holeboard and Morris water maze. We investigated the effect of carnosine on cognitive processes in brain in the settings unrelated to the action of damaging factors. Carnosine administration prevented the increase of lipid hydroperoxides levels and increased the antioxidative state of the brain in rats under development of active avoidance response in the shuttle box. In these settings the acceleration of habit development and the increase in ratio of successfully trained animals was reported. At the same time the level of glutamate—the main transmitter amino acid related to the function of brain’s flexibility—in the brain of rats receiving carnosine increased. The results obtained indicate the nootropic properties of carnosine.