Molecular pattern of a decrease in the rewarding effect of cocaine after an escalating-dose drug regimen.

Background: Long-term cocaine exposure leads to dysregulation of the reward system and initiates processes that ultimately weaken its rewarding effects. Here, we studied the influence of an escalating-dose cocaine regimen on drug-associated appetitive behavior after a withdrawal period, along with corresponding molecular changes in plasma and the prefrontal cortex (PFC).

Methods: We applied a 5 day escalating-dose cocaine regimen in rats.

The effects of the recurrent social isolation stress on fear extinction and dopamine D receptors in the amygdala and the hippocampus.

Background: The present study assessed the influence of recurrent social isolation stress on the aversive memory extinction and dopamine D receptors (DR) expression in the amygdala and the hippocampus subnuclei. We also analyzed the expression of epigenetic factors potentially associated with fear extinction: miRNA-128 and miRNA-142 in the amygdala.

Methods: Male adult fear-conditioned rats had three episodes of 48 h social isolation stress before each fear extinction session in weeks intervals.

The role of the dorsal hippocampus in resistance to the development of posttraumatic stress disorder-like behaviours.

This study aimed to determine the activity of the dorsal hippocampus (dHIP) in resistance to the development of posttraumatic stress disorder (PTSD)-like behaviours. Rats were divided into resistant, PTSD(-), and susceptible, PTSD(+) groups based on the time spent in the central area in an open field test and freezing duration during exposure to an aversive context one week after stress experience (electric foot shock). The PTSD(-) rats, compared to the PTSD(+) group, had an increased concentration of corticosterone in plasma and changes in the activity of the dHIP, specifically, increased c-Fos expression in the dentate gyrus (DG) and increased Neuroligin-2 (marker of GABAergic neurotransmission) expression in the DG and CA3 area of the dHIP.

Sex-Related Predisposition to Post-Traumatic Stress Disorder Development-The Role of Neuropeptides.

Post-traumatic stress disorder (PTSD) is characterized by re-experiencing a traumatic event, avoidance, negative alterations in cognitions and mood, hyperarousal, and severe functional impairment. Women have a two times higher risk of developing PTSD than men. The neurobiological basis for the sex-specific predisposition to PTSD might be related to differences in the functions of stress-responsive systems due to the interaction between gonadal hormones and stress peptides such as corticotropin-releasing factor (CRF), orexin, oxytocin, and neuropeptide Y.

Individual susceptibility or resistance to posttraumatic stress disorder-like behaviours.

The aim of this study was to explore the neurobiological background of individual susceptibility and resistance to the development of posttraumatic stress disorder (PTSD)-like behaviours. Rats were divided into susceptible, PTSD(+), and resistant, PTSD(-), groups based on freezing duration during exposure to aversive context and the time spent in the central area in open field test one week after threefold stress experience (modified single prolonged stress). PTSD(-) rats showed increased concentrations of corticosterone in plasma and changes in GAD67 expression: decreased in the infralimbic cortex (IL) and increased in the lateral amygdala (LA), dentate gyrus (DG), and CA1 area of the hippocampus.

Stress changes amphetamine response, D2 receptor expression and epigenetic regulation in low-anxiety rats.

The aim of this study was to assess the influence of chronic restraint stress on amphetamine (AMPH)-related appetitive 50-kHz ultrasonic vocalisations (USVs) in rats differing in freezing duration in a contextual fear test (CFT), i.e. HR (high-anxiety responsive) and LR (low-anxiety responsive) rats.

Differences in the dopaminergic reward system in rats that passively and actively behave in the Porsolt test.

The aim of the study was to assess appetitive responses and central dopaminergic neurotransmission in passive and active rats divided according to their immobility time in the Porsolt swim test and exposed to restraint stress. Passive rats had more episodes of appetitive 50-kHz ultrasonic vocalization (USV) during rat encounter after social isolation and spent significantly more time in the amphetamine-associated context in conditioned place preference test, compared to active rats. Restraint stress decreased sucrose preference, but increased appetitive vocalization and reinforced the conditioned place preference only in passive animals that was associated with increased dopamine concentration in the amygdala.

The effect of a corticotropin-releasing factor receptor 1 antagonist on the fear conditioning response in low- and high-anxiety rats after chronic corticosterone administration.

This study aimed to test the hypothesis that high-anxiety (HR) rats are more sensitive to the effects of chronic corticosterone administration and antalarmin (corticotropin-releasing factor (CRF) receptor 1, CRF antagonist) injections than low-anxiety (LR) rats, and this effect is accompanied by changes in CRF system activity in brain regions involved in the control of emotions and the hypothalamic-pituitary-adrenal (HPA) axis. Male rats were divided into LR (n = 25) and HR (n = 30) groups according to the duration of conditioned freezing in a contextual fear test. Chronic corticosterone administration (by injection, 20 mg/kg) for 21 d (except weekends) increased freezing duration and number of GR (glucocorticoid receptor)-immunoreactive nuclei in the basal amygdala (BA) and decreased GR-immunoreactive nuclei in the infralimbic cortex (IL), dentate gyrus (DG), and CA3 area, only in the HR group.

Dopaminergic system activity under stress condition - seeking individual differences, preclinical studies.

Dopaminergic system activity in limbic structures (reward system) is related to motivational processes and adaptation to changing environmental conditions. Stress conditions can cause dopaminergic dysfunction, reduce motivational processes and induce compensatory drug use. The susceptibility to stress is characterized by individual variability.

The amphetamine-associated context exerts a stronger motivational effect in low-anxiety rats than in high-anxiety rats.

This study used the conditioned place preference test to explore the effects of subchronic amphetamine administration on drug-associated cues in rats with different emotional reactivity. We also examined the changes in markers of dopaminergic activity in brain regions in response to the amphetamine-paired context, after a withdrawal period preceded by subchronic amphetamine treatment. We used low-anxiety (LR) and high-anxiety (HR) rats, which are known to exhibit distinct levels of susceptibility to amphetamine.

The co-expression of GluN2B subunits of the NMDA receptors and glucocorticoid receptors after chronic restraint stress in low and high anxiety rats.

The aim of this study was to assess the mechanisms underlying behavioural differences between high- (HR) and low- (LR) anxiety rats, selected according to their behaviour in the contextual fear test (i.e., the duration of the freezing response was used as a discriminating variable), after a chronic restraint procedure (21days, 3h daily).

Low-anxiety rats are more sensitive to amphetamine in comparison to high-anxiety rats.

This study utilised the two injection protocol of sensitisation (TIPS) and the conditioned place preference test to validate and extend previous findings on the effects of amphetamine on positive reinforcement-related 50 kHz ultrasonic vocalisation (USV) in rats. We also examined changes in the expression of c-Fos and the NMDA receptor 2B (GluN2B) subunit, markers of neuronal activity and plasticity, in brain regions of rats in response to TIPS. We used low anxiety-responsive (LR) and high anxiety-responsive (HR) rats, which are known to exhibit different fear-conditioned response strengths, different susceptibilities to amphetamine in the TIPS procedure and different amphetamine-dependent 50 kHz USV responses.

Non-parametric analysis of neurochemical effects and Arc expression in amphetamine-induced 50-kHz ultrasonic vocalization.

A number of studies have identified the importance of dopaminergic, opioid, serotonergic, noradrenergic and glutamatergic neurotransmission in amphetamine-induced "50-kHz" ultrasonic vocalizations (USVs). Amphetamine became a topic of interest for many researchers interested in USVs due to its ability to induce 50-kHz USVs. To date, it has been difficult to identify the neurotransmitters responsible for this phenomenon.

Behavioral effects and CRF expression in brain structures of high- and low-anxiety rats after chronic restraint stress.

The aim of our study was to investigate the influence of chronic restraint stress (5 weeks, 3h/day) on behavior and central corticotropin-releasing factor (CRF) expression in rats selected for high (HR) and low anxiety (LR). The conditioned freezing response was used as a discriminating variable. Moreover, we assessed the influence of acute restraint on CRF expression in the brain in HR and LR rats.

GABAergic control of the activity of the central nucleus of the amygdala in low- and high-anxiety rats.

The aim of this study was to examine the role of GABAergic neurotransmission in amygdala nuclei in low- (LR) and high-anxiety (HR) rats after repeated corticosterone administration and acute injection of the benzodiazepine midazolam. The animals were divided into LR and HR groups based on the duration of their conditioned freezing in a contextual fear test (CFT). Repeated daily administration of corticosterone (20 mg/kg s.

N-acetyl cysteine does not modify the sensitization of the rewarding effect of amphetamine as assessed with frequency-modulated 50-kHz vocalization in the rat.

A satisfactory pharmacological cure for addictions to psychostimulants has not yet been developed. Because of the well-known role of changes in the corticoaccumbal and corticostriatal glutamatergic system(s) in drug seeking and relapses in psychostimulant addiction, much hope is presently linked to the use of agents that restore glutamate homeostasis. In this regard, one of the most promising agents is N-acetyl cysteine, which has been shown to reverse some changes in neuroplasticity associated with psychostimulant addiction/dependence.

Chronic restraint increases apoptosis in the hippocampus of rats with high responsiveness to fear stimuli.

This study examined the effects of chronic restraint stress and corticosterone treatment on the apoptosis-related processes in the dentate gyrus of the rat hippocampus. This study compared high (HR) and low anxiety rats (LR) (as defined by their behaviour during the contextual fear test, i.e.

Midazolam treatment before re-exposure to contextual fear reduces freezing behavior and amygdala activity differentially in high- and low-anxiety rats.

The aim of this study was to examine the effects of benzodiazepine (midazolam) administration on rat conditioned fear responses and on local brain activity (c-Fos and CRF expressions) of low- (LR) and high- (HR)anxiety rats after the first and second contextual fear test sessions. The animals were divided into LR and HR groups based on the duration of their conditioned freezing response in the first contextual fear test. The fear-re-conditioned LR and HR animals (28 days later) had increased freezing durations compared with those durations during the first conditioned fear test.

κ-opioid receptor as a key mediator in the regulation of appetitive 50-kHz ultrasonic vocalizations.

Rationale: Acute administration of high doses of morphine reduced 50-kHz ultrasonic vocalizations (USVs). Although morphine meets the classical criteria for inducing 50-kHz USVs (it causes place preference and induces dopamine release in nucleus accumbens), it also inhibits appetitive vocalizations.

Objective: The aims of this study were to (i) study the pharmacological impact of κ-opioid (KOR) and μ-opioid receptor (MOR) ligands on the emission of 50-kHz USVs triggered by social interaction after long-term isolation and (ii) analyze the concentrations of the main neurotransmitters in reward-related structures (ventral tegmental area (VTA), nucleus accumbens (NAcc), and medial prefrontal cortex (mPFC)).

High-anxiety rats are less sensitive to the rewarding affects of amphetamine on 50kHz USV.

This study assessed behaviour, as measured by 50kHz calls related to positive affect, in rats with different fear conditioned response strengths: low-anxiety rats (LR) and high-anxiety rats (HR), after amphetamine injection in a two-injection protocol (TIPS). The results showed that the first dose of amphetamine evoked similar behavioural effects in frequency-modulated (FM) 50kHz calls in the LR and HR groups. The second injection of amphetamine resulted in stronger FM 50kHz calls in LR compared with HR rats.

Altered glutamate/GABA equilibrium in aged mice cortex influences cortical plasticity.

Age-related molecular changes in the synapse can cause plasticity decline. We found an impairment of experience-dependent cortical plasticity is induced by short lasting sensory conditioning in aged mice. However, extending the training procedure from 3 to 7 days triggered plasticity in the aged cortex of the same range as in young mice.

The effect of chronic administration of corticosterone on anxiety- and depression-like behavior and the expression of GABA-A receptor alpha-2 subunits in brain structures of low- and high-anxiety rats.

The aim of this study was to examine changes in rat emotional behavior and determine differences in the expression of GABA-A receptor alpha-2 subunits in brain structures of low- (LR) and high-anxiety (HR) rats after the repeated corticosterone administration. The animals were divided into LR and HR groups based on the duration of their conditioned freezing in a contextual fear test. Repeated daily administration of corticosterone (20 mg/kg) for 21 days decreased activity in a forced swim test, reduced body weight and decreased prefrontal cortex corticosterone concentration in both the LR and HR groups.

Changes in the brain expression of alpha-2 subunits of the GABA-A receptor after chronic restraint stress in low- and high-anxiety rats.

This study assessed the mechanisms underlying the behavioral differences between high- (HR) and low-anxiety (LR) rats selected for their behavior in the contextual fear test (i.e., the duration of the freezing response was used as a discriminating variable).

Changes in the Egr1 and Arc expression in brain structures of pentylenetetrazole-kindled rats.

Background: Epileptogenesis is regarded as a complicated and relatively poorly understood phenomenon. Some of immediate early genes (IEGs) as egr1 (zif268) or arc (arg3.1) are believed to play an important role in the process of epileptogenesis.

Inter-individual diversity and intra-individual stability of amphetamine-induced sensitization of frequency-modulated 50-kHz vocalization in Sprague-Dawley rats.

Rationale: Propensity for drug dependence shows great diversity that is related to intrinsic neurobiological factors. This diversity is important both for the understanding of these traits and for the development of therapies.

Objectives: The goals of the study were (1) to define, using ultrasonic vocalization characteristics, inter-individual differences in rats' propensity for sensitization to amphetamine, (2) to test whether possible resistance to this effect could be overcome with repetitive treatment, and (3) to seek useful predictors of the propensity.