Behavioral neuroscience最新文献

Prodromal signs of Parkinson's disease (PD), including vocal communication deficits, are poorly understood and do not respond adequately to current pharmacologic treatments. Norepinephrine dysfunction is involved early in PD; thus, drug therapies targeting norepinephrine may be useful as a treatment of prodromal signs. This study used a validated, translational rodent model of prodromal PD, the male Pink1-/- rat, which exhibits ultrasonic vocalization (USV) deficits as early as 2 months of age. The purpose of this preclinical study was to investigate a dose-dependent (2.5, 5.0, 7.5, 10 mg/kg) response of methylphenidate on USV parameters with the hypothesis that methylphenidate would increase vocalization output. Because methylphenidate is a psychostimulant with known adverse side effects, we also hypothesized that potential side effects including anxietylike behavior and spontaneous activity would be increased in a dose-dependent manner. To accomplish this, wild-type (WT) and Pink1-/- rats were administered a dose of a vehicle (saline) and a methylphenidate dose in a randomized within-subjects design and then assessed for USVs, anxiety behavior (open field), and limb motor (cylinder) activity. The results suggest that methylphenidate does not alter USV emissions in Pink1-/- rats; however, methylphenidate increased the total number of vocalizations and duration of frequency-modulated calls in WT rats. Methylphenidate dose dependently influenced spontaneous movements in both WT and Pink1-/- rats, as expected, while methylphenidate increased anxiety in Pink1-/- rats and not WT rats. This study demonstrates a difference in response to a psychostimulant between Pink1-/- rats and WT rats. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Slight and hidden hearing loss in children have been linked to cognitive and social difficulties, and yet the neurobiological mechanisms behind these issues remain poorly understood. Most animal models focus on severe hearing loss, leaving the effects of hidden or slight hearing loss largely unexplored. To uncover the neural mechanisms connecting slight/hidden hearing loss to cognitive and social challenges, we induced hearing loss in young (4-week-old) Wistar rats through noise exposure. We then examined cognitive function (object recognition test) and social behavior (juvenile play behavior and social interaction). Changes in brain anatomy were assessed using cortical thickness and hippocampal size measurements, while (immuno)histochemical staining investigated neuronal circuitry maturation (myelin basic protein, parvalbumin, and perineuronal nets) and neurogenesis (doublecortin). Noise-exposed rats displayed slight high-frequency hearing loss (around 20 dB) and hidden hearing loss at other tested frequencies. This slight/hidden hearing loss was associated with impaired object recognition but did not alter social behavior. Slight/hidden hearing loss was associated with reduced myelin basic protein expression in the corpus callosum but no other alterations in cortical thickness, hippocampal size, or other markers of maturation and neurogenesis were found. These findings show that even slight/hidden hearing loss can lead to subtle brain alterations tied to cognitive deficits. This study emphasizes the need for further research to fully understand the brain changes associated with slight/hidden hearing loss and to pinpoint the mechanisms connecting these changes to behavioral deficits. This information is crucial to develop interventions to prevent the cognitive and social consequences of hearing loss. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

An N-protected methylenedioxymethamphetamine (MDMA), N-tert-butoxycarbonyl-3,4-methylenedioxymethamphetamine (t-BOC-3,4-MDMA), contains tert-butoxycarbonyl and can remain undetected in the illicit drug market. It is a new type of precursor substance that is not a chemical intermediate and can be converted into a controlled substance, MDMA, by deprotection of the N-tert-butoxycarbonyl group. Categorization of this chemical into a precursor or psychotropic substance is an issue because it is an unprecedented precursor that could have misuse potential. Although MDMA causes rewarding and reinforcing effect through dopaminergic transmission, the misuse potential of t-BOC-3,4-MDMA has not yet been characterized. Here, we aim to evaluate the misuse potential of t-BOC-3,4-MDMA. The response to the drug at a dose of 5 mg/kg was determined by a climbing test, and its rewarding and reinforcing properties were assessed through conditioned place preference and self-administration tests. In the conditioned place preference test, intraperitoneal administration of t-BOC-3,4-MDMA (5 mg/kg) significantly altered place preference in mice. In the self-administration models, t-BOC-3,4-MDMA induced drug-taking behavior at the dose of 0.5 mg/kg/infusion (intravenous) during 2 hr sessions under fixed-ratio schedules in mice. In addition, microdialysis experiments verified that t-BOC-3,4-MDMA impacted the dopamine levels of the brain (striatum) of rats. These experimental results indicate that t-BOC-3,4-MDMA has a potential for misuse. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The n-back task has been widely used to study working memory. Previous studies investigating the electrophysiological (electroencephalogram [EEG]) and hemodynamic correlates (functional near-infrared spectroscopy [fNIRS]) of the n-back task have been generally based on verbal stimuli and only investigated EEG frequency bands. We simultaneously acquired the EEG and fNIRS in 35 participants (16 males; age = 26.4 ± 4.3 years; educational attainment = 18 ± 2 years) during a visuospatial n-back task. The task encompassed a control condition and a low (requiring to recall one previous stimulus) and a high (requiring to recall two previous stimuli) working memory load experimental conditions. Accuracy decreased and reaction times slowed in the high compared to both low load and control conditions. Regarding EEG, P3a showed higher amplitude in the experimental conditions compared to the control one, and P3b exhibited higher amplitude in the low compared to the high load condition. Regarding fNIRS, the high load condition showed higher deoxygenated hemoglobin compared to the control one. Moreover, the central frontopolar cortex showed higher activation compared with the left frontal cortex. Our study showed that working memory load during a visuospatial n-back task influenced behavioral and electrophysiological indices. Even if the load effect was only observed for deoxygenated hemoglobin on hemodynamic data, this was in line with previous studies and coherent with its electrophysiological correlates. Thus, our study confirms that EEG and fNIRS can be successfully used in multimodal acquisitions, but also highlights that future studies are needed to develop a novel version of the task. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Pavlovian extinction reduces the performance of conditioned responses and occurs when the conditioned stimulus (CS) is repeatedly presented in the absence of the unconditioned stimulus (US). However, when the CS is experienced in a context that is different from the extinction context, there is a recovery of the conditioned response, a phenomenon known as renewal. There is some evidence that the renewal of appetitive conditioning is influenced by sex, with females failing to exhibit renewed responding. Further, there is recent evidence that renewal of fear might also not occur in female rats. In both appetitive and fear preparations, the lack of renewal in females has been postulated to be related to cycling ovarian hormones. Therefore, in Experiments 1 and 2, we directly compared fear renewal in males and females (Experiment 1) as well as ovariectomized (OVX) females (Experiment 2) when conditioning occurred in Context A, extinction in B, and testing in A (ABA renewal). Experiments 3 and 4 examined renewal when conditioning and extinction occurred in A and testing occurred in B (AAB renewal). In all experiments, renewal was not significantly different between male and female rats. Further, in Experiments 2 and 4, renewal did not differ between males, intact females, and OVX females. Additionally, in each experiment, there was no evidence that context excitation and/or inhibition contributed to renewal; instead suggesting that renewal was controlled by an occasion-setting mechanism. Overall, these results suggest little evidence for the role of sex in renewal of conditioned freezing and also indicate that cycling ovarian hormones have little role in the strength of renewal in female rats. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Social isolation can have long-term effects on brain development and behavior and increases the risk of developing clinical conditions, including anxiety disorders. One modulator of the stress response is gamma-aminobutyric acid, an inhibitory neurotransmitter synthesized by glutamic acid decarboxylase (GAD). This study examined sex differences in behavior and GAD expression following prolonged social isolation beginning in adolescence in Long Evans rats. Males and females were equally divided into group-housed (GH) and socially isolated conditions on Postnatal Day 28 (n = 8 per group). Beginning 5 weeks later, tests were conducted for anxietylike behaviors (open-field test and elevated plus maze), social interactions (sociability test), and spatial memory (novel object location). Sex differences in behavior were observed, with GH females showing fewer anxietylike behaviors in the open-field test and elevated plus maze and spending more time with objects (sociability task) compared to GH males. Isolation had no effect on males but increased anxiety and reduced neophilic measures in females, removing sex differences. On the sociability task, all groups spent more time with novel rats compared to objects, suggesting social interest was retained after isolation. In the hippocampus, isolation reduced GAD in both sexes, and sex differences were seen (F > M). However, no group differences in behavior were observed in the hippocampal-dependent novel object location task. Our findings suggest that prolonged social isolation beginning in adolescence is anxiogenic for female Long Evans rats. Furthermore, sex and housing impact hippocampal GABA-ergic activity, which may have important implications in the treatment of anxiety disorders. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Dietary maternal deficiency in omega-3 polyunsaturated fatty acids (n-3 PUFA) is a potential risk factor for the development of anxiety and other mood disorders in children and adolescents. Here, we used a previously characterized maternal n-3 PUFA dietary deficiency model in rats to determine the impact of postweaning supplementation on adolescent anxiety-like behaviors. We focused on two models of anxiety: innate anxiety tested by the elevated plus maze and a novel operant model of learned anxiety where animals learn that actions may be associated with a variable probability of harm. Given that recent basic and clinical studies have associated anxiety and other adverse effects of n-3 PUFA deficiency on inflammatory processes and microglial structure and function, we also assessed the impact of our dietary deficiency model and supplementation on adolescent microglial morphology in multiple brain regions. We found that the male and female adolescent n-3 PUFA-deficient groups exhibit increased innate anxiety, but only females showed enhanced learned anxiety. Supplementation after weaning did not significantly affect innate anxiety but ameliorated learned anxiety in females. Thus, the beneficial effects of supplementation on adolescent anxiety may be sex-specific and depend on the type of anxiety. We also found that n-3 PUFA deficiency influences microglia function in adolescents in the amygdala and nigrostriatal, but not mesolimbic, brain regions. Collectively, these data suggest that while n-3 PUFA dietary supplementation may be effective in reducing adolescent anxiety, this effect is context-, sex-, and brain network-specific. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The reconsolidation hypothesis posits that memory retrieval initiates a phase of memory destabilization, followed by restabilization through protein synthesis-dependent processes. The disruption of reconsolidation by amnestic agents can lead to memory loss. Yet, this hypothesis leaves unanswered questions regarding the mechanisms driving amnesia induction and reversal of molecular and structural changes underlying memory retention. Our previous work proposed that amnesia induction is an active process reliant on both translation and transcription. To test this hypothesis, we explored the role of N-methyl-D-aspartate (NMDA) glutamate receptors, as well as protein and RNA synthesis in amnesia induction mechanisms in grape snails trained with conditional food aversion, during the initial hours following memory reconsolidation disruption. Our results reveal that protein synthesis inhibitor administration before the conditioned reminder stimulus caused amnesia 3 hr after the reminder, whereas NMDA glutamate receptor antagonists resulted in amnesia less than 20 min following the first conditioned reminder stimulus. Concurrent administration of an NMDA receptor antagonist and a protein synthesis inhibitor before the reminder resulted in a rapid (less than 20 min) and complete prevention of amnesia, underscoring the pivotal role of protein synthesis in NMDA-dependent amnesia induction. Conversely, RNA synthesis inhibitors did not affect memory reconsolidation but inhibited amnesia triggered by an NMDA receptor antagonist. Moreover, our study demonstrates a significant difference in the dependency of memory reconsolidation and amnesia induction "time windows" on protein synthesis. These findings lend support to our hypothesis that memory reconsolidation and amnesia represent distinct processes, each characterized by unique developmental dynamics and molecular underpinnings. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Healthy cognition requires inhibitory modulation of associative learning; conversely, impaired inhibitory discrimination is implicated in behavioral disorders. The medial prefrontal cortex (mPFC) and its dopamine innervation are key to understanding inhibition and impulsivity. We therefore examined the role of prelimbic and infralimbic cortices in within-subjects appetitive feature-negative learning using microinfusions of (a) the gamma-aminobutyric acid-A receptor agonist muscimol (0.25 μg in 1.0 μl; N = 35), (b) the dopamine D1 receptor agonist SKF-81297 (0.1 μg in 1.0 μl; N = 33), and (c) the dopamine D1 receptor antagonist SCH-23390 (5 μg in 1.0 μl; N = 35). A conditioned stimulus (CS) was followed by food, but on trials on which the CS (A+) was compounded with the inhibitory cue (AX-), the food delivery was canceled. Difference scores (CS-preCS responding) were used to measure learning. All three experiments showed the feature-negative discrimination (A+/AX-), as decreased responding to AX- versus A+. This discrimination was reduced but preserved following muscimol infusions in Experiment 1. Similarly, in Experiments 2 and 3, infusions of SKF-81297 and SCH-23390 were both without effect on the acquisition of the discrimination. Like muscimol, SCH-23390 reduced difference score responding, consistent with nonspecific effects on the (expression of) learning. Thus, there was no evidence to suggest that inactivation of prelimbic or infralimbic cortices impaired feature-negative discrimination learning and no evidence for dopaminergic modulation of such learning in the medial prefrontal cortex either. These results are discussed in the context of the nonspecific effects of the infusions and the overall inconsistent performance in summation and retardation tests of conditioned inhibition. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Individuals diagnosed with stress-related psychiatric disorders in adulthood are likely to have experienced early life stress, suggesting that early adversity is an important vulnerability factor in the subsequent development of trauma- and anxiety-related psychiatric illness. It is important to develop animal models of psychiatric dysfunction to determine evident vulnerability considerations, potential biomarkers, and novel treatment avenues to improve the human condition. In our model of acute early life stress (aELS), 15 footshocks are delivered in a single session on postnatal day 17. The following experiments investigated the persistent impacts of our aELS procedure on stress-enhanced fear learning, anxiety-related behaviors, maintenance of fear, and resistance to extinction in adult male and female rats. The findings from these experiments demonstrate that our aELS procedure yields enhanced fear learning and increased anxiety. This enhanced fear is maintained over time, yet it extinguishes normally. Taken together, these results demonstrate that exposure to 15 footshocks during a single session early in life (postnatal day 17) recapitulates a number of important features of trauma- and anxiety-related disorder symptomatology, but not others. Future studies are needed to determine the persistent physiological phenotypes resulting from aELS and the neurobiological mechanisms that mediate these long-term changes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).