Operant Chamber Research Articles

Acute vagus nerve stimulation enhances reversal learning in rats

Cognitive flexibility is a prefrontal cortex-dependent neurocognitive process that enables behavioral adaptation in response to changes in environmental contingencies. Electrical vagus nerve stimulation (VNS) enhances several forms of learning and neuroplasticity, but its effects on cognitive flexibility have not been evaluated. In the current study, a within-subjects design was used to assess the effects of VNS on performance in a novel visual discrimination reversal learning task conducted in touchscreen operant chambers. The task design enabled simultaneous assessment of acute VNS both on reversal learning and on recall of a well-learned discrimination problem. Acute VNS delivered in conjunction with stimuli presentation during reversal learning reliably enhanced learning of new reward contingencies. Enhancement was not observed, however, if VNS was delivered during the session but was not coincident with presentation of to-be-learned stimuli. In addition, whereas VNS delivered at 30 HZ enhanced performance, the same enhancement was not observed using 10 or 50 Hz. Together, these data show that acute VNS facilitates reversal learning and indicate that the timing and frequency of the VNS are critical for these enhancing effects. In separate rats, administration of the norepinephrine reuptake inhibitor atomoxetine also enhanced reversal learning in the same task, consistent with a noradrenergic mechanism through which VNS enhances cognitive flexibility.

Inhibition of AMPA receptors (AMPARs) containing transmembrane AMPAR regulatory protein γ-8 with JNJ-55511118 shows preclinical efficacy in reducing chronic repetitive alcohol self-administration.

A prominent therapeutic indication for alcohol use disorder (AUD) is reduction in chronic repetitive alcohol use. Glutamate α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPARs) regulate chronic alcohol self-administration in preclinical models. Recent evidence indicates that the expression and function of AMPARs require the transmembrane AMPAR regulatory protein γ-8 (TARP γ-8). This study evaluated the preclinical efficacy of JNJ-55511118, a novel, selective, high-affinity inhibitor of TARP γ-8-bound AMPARs, in reducing chronic operant alcohol self-administration. Separate groups of male and female C57BL/6J mice (n=8/sex/group) were trained to lever press for sweetened alcohol (9% v/v+sucrose 2% w/v) or sucrose only (2% w/v) in operant conditioning chambers using an FR-4 schedule of reinforcement. After a 40-day baseline, JNJ-55511118 (0, 1, and 10mg/kg, p.o.) was administered in randomized order 1 h before self-administration sessions. Parameters of operant behavior including response rate, total reinforcers, and head entries in the drinking troughs were computer recorded. During baseline, responding to alcohol, but not sucrose, was greater in female than male mice. In male mice, both doses of JNJ-55511118 decreased multiple parameters of alcohol self-administration but did not reduce behavior-matched sucrose-only self-administration. JNJ-55511118 had no effect on sweetened alcohol or sucrose self-administration in female mice. Subsequent tests of motor function showed that the lowest effective dose of JNJ-55511118 (1mg/kg) had no effect on open-field activity in male mice. This study shows for the first time that TARP γ-8-bound AMPARs regulate a behavioral pathology associated with addiction. The preclinical efficacy of JNJ-55511118 in reducing alcohol self-administration in male mice suggests that inhibition of TARP γ-8-bound AMPARs is a novel and highly significant neural target for developing medications to treat AUD and other forms of addiction.

Scaling N from 1 to 1,000,000: Application of the Generalized Matching Law to Big Data Contexts.

The generalized matching law (GML) has been used to describe the behavior of individual organisms in operant chambers, artificial environments, and nonlaboratory human settings. Most of these analyses have used a handful of participants to determine how well the GML describes choice in the experimental arrangement or how some experimental manipulation influences estimated matching parameters. Though the GML accounts very well for choice in a variety of contexts, the generality of the GML to all individuals in a population is unknown. That is, no known studies have used the GML to describe the individual behavior of all individuals in a population. This is likely because the data from every individual in the population has not historically been available or because time and computational constraints made population-level analyses prohibitive. In this study, we use open data on baseball pitches to provide an example of how big data methods can be combined with the GML to: (1) scale within-subjects designs to the population level; (2) track individual members of a population over time; (3) easily segment the population into subgroups for further analyses within and between groups; and (4) compare GML fits and estimated parameters to performance. These were accomplished for each of 2,374 individuals in a population using 8,467,473 observations of behavior-environment relationships spanning 11 years. In total, this study is a proof of concept for how behavior analysts can use data-science techniques to extend individual-level quantitative analyses of behavior to the population-level focused on domains of social relevance.

ACE Inhibitor, Lisinopril, Affects Age‐Associated Changes in Cardiovascular and Cognitive Function in Female Dahl Salt‐Sensitive Rats

Background Aged Dahl Salt-Sensitive (DSS) rats develop central arterial stiffness (CAS) and hypertension on a normal salt (NS) diet. These changes have effects on cognition via brain structural changes associated with CAS. Previous results showed that ACE inhibitor lisinopril (Lis) improved cardiovascular and cognitive function in male DSS rats. Here we determined whether these effects of Lis on physiology and behavior could be achieved in age-matched female DSS rats. Methods Female DSS rats (n=23) were kept on a NS diet (0.5% NaCl) for the duration of the study. Baseline (BL) measurements were taken at 3- and 6-mo of age. After 6-mo measurements, rats were given either Lis in drinking water (15mg/kg/day, n=12) or control treatment (n=11). Final measurements were taken after 7-mo of Lis treatment, before tissues were collected for histochemistry using Verhoeff's stain for collagen and elastin. Systolic blood pressure (SBP) was measured using tail-cuff plethysmography. Pulse wave velocity (PWV), a measure of CAS, was measured by echocardiography. Open field test (OFT) was performed to assess anxiety-like behavior, and Morris water maze (MWM) was performed to assess spatial memory function. Rats were tested in an operant chambers attention challenge to assess attention and impulsivity. Statistical analyses were performed using Pearson correlation and 2-way ANOVA mixed effects model. Data are presented as mean ± SEM. Results At 3 and 6-mo of age, the treatment groups did not display differences in SBP or PWV. Following treatment, the Lis treated rats had lower SBP vs. controls (116 ± 3.7 vs. 187 ± 9.5 mmHg; p<0.01). Similarly, PWV was lower at 13-mo in treated vs. control rats (4.4 ± 0.3 vs. 5.7 ± 1.0 m/s; p<0.05) (Fig. 1A-B). Histochemical analysis revealed that the aortic media collagen abundance, a measure of fibrosis, was lower (18.5 ± 0.9% vs. 21.5 ± 0.8%, p<0.05) and the elastin/collagen ratio in the aortic media of treated rats was higher (2.5 ± 0.1 vs. 2.0 ± 0.1, p<0.05) than that of controls (Fig. 1C-D). Performance on the OFT at 13-mo compared to 6-mo BL indicated that the treated group had an increase in activity in the center of the field with age (+25% vs. BL) i.e., lower anxiety levels, while in control rats there was an opposite effect (-32% vs. BL) (Fig. 2A). PWV was negatively correlated with distance traveled in the center of the OFT at 13-mo (R=-0.672, P<0.05). MWM results showed that treated rats traveled a shorter distance to a hidden platform compared to control rats (6.5 ± 0.7 vs. 8.8 ± 0.9 m; p=0.039), indicating better spatial memory in the treated group (Fig. 2B). In the attention test at 13-mo of age, treated rats had more correct and fewer premature responses vs. control rats (Fig. 2C-D). Conclusion Female DSS rats show beneficial effects of Lis on cardiovascular and cognitive function. Lower SBP, reduced aortic fibrosis, and stabilized PWV in Lis treated female DSS rats were associated with improved behavioral test performance. The mechanistic basis of the effects of Lis on cognition via cerebrovascular and brain changes is being further investigated.

Analgesia and Prevention of Opioid Self‐Administration by Agmatine‐Based Analogues

Chronic pain is a debilitating condition that is a heightened health concern due to the concurrent pain and opioid epidemics. The currently available options for the treatment and management of chronic pain, opioids, are associated with risk of conversion to addiction and diversion from patients for whom use is intended. To this end, we have studied non-opioid interventions, specifically the inhibition of the glutamatergic system. The glutamatergic system is shown to play a central role in opioid addiction, therefore its inhibition has been shown to prevent the development of opioid-seeking behavior in a rodent model of drug-seeking. A decarboxylated form of L-arginine, agmatine, is able to prevent the development of fentanyl-seeking behavior in a model of mouse self-administration likely through its role as an N-methyl-D-aspartate antagonist. However, agmatine has shown limited penetration through the blood brain barrier (BBB) and a short systemic half-life, limiting its clinical utility. We have designed a strategically-substituted agmatine compound (SSA3) with the goal of improving its penetration through the BBB by increasing the lipophilicity of agmatine, potentially improving distribution across the BBB and increasing its half-life following systemic delivery. To this end, we have evaluated SSA3 as a more viable potential therapeutic for the treatment of opioid use disorders (OUD). Mice (F, 21-30g) were given access to operant chambers and allowed to press either for oral oxycodone reward or an inactive control. Daily, the mice were given either a pre-treatment of a strategically-substituted agmatine (SSA3) compound or vehicle control, i.p.. Daily lever-pressing was recorded as an indication of drug-seeking behavior. Additionally, this same cohort was allowed to lever press for food pellet reward following conclusion of oxycodone reinforcement. Area under the curve (AUC) was compared between SSA pre-treated and vehicle pre-treated groups. Pre-treatment with the SSA3 compound significantly decreased oxycodone seeking behavior, but had no impact on food-maintained responding. Additionally, SSA3 showed no impact on motor coordination or cardiovascular function, side effects of concern for glutamatergic compounds. These data indicate that a strategically-substituted agmatine compound is capable of significantly reducing opioid-seeking behavior with a wide therapeutic window, avoiding the motor impairment and cardiovascular impairment typical of drugs of this class. Our future work includes optimization of dosing regimen as well as modeling the prevention of opioid relapse.

NLX-101, a cortical 5-HT1A receptor biased agonist, reverses scopolamine-induced deficit in the delayed non-matching to position model of cognition

NLX-101 is a selective, high efficacy, biased agonist at post-synaptic cortical 5-HT1A receptors. We have previously shown that it opposes deficits produced by blockade of NMDA receptors and has pro-cognitive activity of its own. Based on the strong interaction between 5-HT1A receptors and the central cholinergic system, we tested NLX-101 on scopolamine-induced impairment of cognition in a delayed non-matching to position (DNMTP) model. The cholinesterase inhibitor, tacrine, was used as a comparator.In operant chambers with two retractable levers, male rats were trained to press one randomly presented lever during a “sample” phase. Following a time delay of either 1, 5 or 10 s, both levers were then presented, the rat being required to press the correct lever (i.e. the one not previously presented) to receive a food pellet reward.Scopolamine (0.16 mg/kg i.p.) significantly impaired accuracy (i.e. choice of correct lever) at 5 and 10 s delays. In contrast, NLX-101 (0.04, 0.16, 0.63 mg/kg i.p.) did not worsen accuracy, except at 0.63 mg/kg. Moreover, NLX-101 (0.04 and 0.16 mg/kg) dose-dependently and significantly opposed scopolamine-induced impairment for 5 and 10 s delays, with near-total reversal at 10 s. The acetylcholinesterase inhibitor, tacrine, also opposed scopolamine-induced impairment but was less potent and efficacious, with a single significant effect at 2.5 mg/kg and 5 s delay only.The present data suggest that biased agonism at post-synaptic, cortical 5-HT1A receptors could prove useful in neurological or neuropsychiatric pathologies characterized by cognitive deficits consecutive to a reduced central cholinergic tone.

Endocannabinoid signaling in the lateral habenula regulates pain and alcohol consumption

Hyperalgesia, which often occurs in people suffering from alcohol use disorder, may drive excessive drinking and relapse. Emerging evidence suggests that the lateral habenula (LHb) may play a significant role in this condition. Previous research suggests that endocannabinoid signaling (eCBs) is involved in drug addiction and pain, and that the LHb contains core components of the eCBs machinery. We report here our findings in rats subjected to chronic ethanol vapor exposure. We detected a substantial increase in endocannabinoid-related genes, including Mgll and Daglb mRNA levels, as well as monoacylglycerol lipase (MAGL) protein levels, as well as a decrease in Cnr1 mRNA and type-1 cannabinoid receptor (CB1R) protein levels, in the LHb of ethanol-exposed rats. Also, rats withdrawing from ethanol exposure displayed hypersensitivity to mechanical and thermal nociceptive stimuli. Conversely, intra-LHb injection of the MAGL inhibitor JZL184, the fatty acid amide hydrolase inhibitor URB597, or the CB1R agonist WIN55,212-2 produced an analgesic effect, regardless of ethanol or air exposure history, implying that alcohol exposure does not change eCB pain responses. Intra-LHb infusion of the CB1R inverse agonist rimonabant eliminated the analgesic effect of these chemicals. Rimonabant alone elicited hyperalgesia in the air-, but not ethanol-exposed animals. Moreover, intra-LHb JZL184, URB597, or WIN55,212-2 reduced ethanol consumption in both homecages and operant chambers in rats exposed to ethanol vapor but not air. These findings suggest that LHb eCBs play a pivotal role in nociception and facilitating LHb eCBs may attenuate pain in drinkers.

Persistence of Operant Responding for Food After Prior Cocaine Exposure in Fischer 344 But Not Lewis Rats.

Chronic cocaine exposure has differential neural effects in Fischer 344 (F344) vs Lewis inbred rats that may explain strain-dependent differences during acquisition vs maintenance of cocaine self-administration. We assessed whether prior cocaine exposure alters operant responding for food across various phases (acquisition, maintenance, extinction, spontaneous recovery, reinitiation) in these strains. Lewis and F344 rats (N = 12) were administered three cocaine (15 mg/kg) or saline injections at hourly intervals for 3 consecutive days. Beginning the next day for 24 days, rats had access to operant chambers in which one lever depression resulted in the delivery of a food pellet. Then, four extinction sessions were conducted in which food was no longer available, but other stimulus conditions remained the same. After a 2-day break, spontaneous recovery was assessed over four sessions. Food delivery was then restored for 3 days to test reinitiation followed by a progressive ratio session. Lewis rats acquired the operant faster than F344 rats. F344 rats showed lower maintenance rates than Lewis rats but higher spontaneous recovery responding. Cocaine exposure caused persistence of responding during extinction in F344 but not Lewis rats. All groups reinitiated responding when food was available again and did not differ in final ratios completed under the progressive ratio schedule. That prior cocaine exposure led to persistence of responding in F344 rats during extinction may reflect heightened contextual conditioning that interferes with the ability to extinguish responding. Results have implications for the genetic contribution to relapse-like behaviors. (Am J Addict 2021;00:00-00).

Base rates bias performance in a temporal bisection task.

We investigated how base rates affect temporal discrimination. In a temporal bisection task, pigeons learned to choose one key after a short sample and another key after a long sample. When presented with a range of intermediate samples they produced a psychometric function characterized by a bias and a scale parameter. When one of the trained samples was more frequent than the other, only the location parameter changed, with the pigeons biasing their choices toward the key associated with the most frequent sample. We then reproduced the bisection task in a long operant chamber, with choice keys far apart, and tracked the pigeons' motion patterns during the sample. Pigeons learned to approach the short key following sample onset, wait on the "short side" for a few seconds, and then, when the sample continued, depart toward the long key. This time-place curve was affected by sample base rate: The probability of pigeons going directly to the long side after sample onset increased when long samples were more frequent than short samples, indicating a decrease of temporal control. We found no evidence of changes in temporal sensitivity. The results are most consistent with models of timing that take into account biasing effects and competition for stimulus control. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Maternal Serum Inhibin-A Augments the Value of Maternal Serum PlGF and of sFlt-1/PlGF Ratio in the Prediction of Preeclampsia and/or FGR Near Delivery—A Secondary Analysis

Objective: We previously provided evidence to confirm that maternal serum levels of soluble Fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and their ratio are useful tools to direct the management of preeclampsia (PE), fetal growth restriction (FGR), and PE+FGR near delivery. In this secondary analysis, we further examine the potential additive value of maternal serum Inhibin-A, which is a hormone marker of the transforming growth factor family, to the accuracy provided by maternal serum PlGF and sFlt-1. Methods: We conducted a secondary analysis where we extracted the data of a cohort of 125 pregnant women enrolled near delivery at the clinics of the University Medical Center of Ljubljana, Slovenia. The dataset included 31 cases of PE, 16 of FGR, 42 of PE+FGR, 15 preterm delivery (PTD), and 21 unaffected controls with delivery of a healthy baby at term. Cases delivered before 34 weeks’ gestation included 10 of PE, 12 of FGR, 28 of PE+FGR, and 6 of PTD. In addition to the recorded demographic characteristics and medical history and the maternal serum levels of PlGF and sFlt-1/PlGF ratio, which were previously published, we evaluated the added value of maternal serum Inhibin-A. The predictive accuracy of each biomarker, their ratios, and combinations were estimated from areas under the curve (AUC) of receiver operating characteristics (ROC) curves, Box and Whisker plots, and by multiple regression. We estimated accuracy by the continuous marker model and a cutoff model. Results: In this study, we combined Inhibin-A with PlGF or with the sFlt-1/PlGF ratio and showed a 10–20% increase in AUCs and 15–45% increase in the detection rate, at 10% false positive rate, of PE, and a lower, but significant, increase for PE+FGR and FGR in all cases but not for FGR in early cases delivered &lt; 34 weeks. The use of a cutoff model was adequate, although a bit higher accuracy was obtained from the continuous model. The highest correlation was found for PlGF with all three complications. Conclusion: In this secondary analysis, we have found that maternal serum Inhibin-A improves the accuracy of predicting PE and PE+FGR provided by maternal serum angiogenic markers alone, bringing the results to a diagnostic level; thus, it could be considered for directing clinical management. Inhibin-A had smaller or no added value for the accuracy of predicting FGR alone, mainly of early cases delivered &lt;34 weeks.

A computational reward learning account of social media engagement

Social media has become a modern arena for human life, with billions of daily users worldwide. The intense popularity of social media is often attributed to a psychological need for social rewards (likes), portraying the online world as a Skinner Box for the modern human. Yet despite such portrayals, empirical evidence for social media engagement as reward-based behavior remains scant. Here, we apply a computational approach to directly test whether reward learning mechanisms contribute to social media behavior. We analyze over one million posts from over 4000 individuals on multiple social media platforms, using computational models based on reinforcement learning theory. Our results consistently show that human behavior on social media conforms qualitatively and quantitatively to the principles of reward learning. Specifically, social media users spaced their posts to maximize the average rate of accrued social rewards, in a manner subject to both the effort cost of posting and the opportunity cost of inaction. Results further reveal meaningful individual difference profiles in social reward learning on social media. Finally, an online experiment (n = 176), mimicking key aspects of social media, verifies that social rewards causally influence behavior as posited by our computational account. Together, these findings support a reward learning account of social media engagement and offer new insights into this emergent mode of modern human behavior.

Using touchscreen equipped operant chambers to study animal cognition. Benefits, limitations, and advice.

Operant chambers are small enclosures used to test animal behavior and cognition. While traditionally reliant on simple technologies for presenting stimuli (e.g., lights and sounds) and recording responses made to basic manipulanda (e.g., levers and buttons), an increasing number of researchers are beginning to use Touchscreen-equipped Operant Chambers (TOCs). These TOCs have obvious advantages, namely by allowing researchers to present a near infinite number of visual stimuli as well as increased flexibility in the types of responses that can be made and recorded. We trained wild-caught adult and juvenile great-tailed grackles (Quiscalus mexicanus) to complete experiments using a TOC. We learned much from these efforts, and outline the advantages and disadvantages of our protocols. Our training data are summarized to quantify the variables that might influence participation and success, and we discuss important modifications to facilitate animal engagement and participation in various tasks. Finally, we provide a "training guide" for creating experiments using PsychoPy, a free and open-source software that was incredibly useful during these endeavors. This article, therefore, should serve as a resource to those interested in switching to or maintaining a TOC, or who similarly wish to use a TOC to test the cognitive abilities of non-model species or wild-caught individuals.

Corticosterone Attenuates Reward-Seeking Behavior and Increases Anxiety via D2 Receptor Signaling in Ventral Tegmental Area Dopamine Neurons.

Corticosteroids (CORT) have been widely used in anti-inflammatory medication. Chronic CORT treatment can cause mesocorticolimbic system dysfunctions, which are known to play a key role for the development of psychiatric disorders. The VTA is a critical site in the mesocorticolimbic pathway and is responsible for motivation and reward-seeking behaviors. However, the mechanism by which chronic CORT alters VTA dopamine neuronal activity is largely unknown. We treated periadolescent male mice with vehicle, 1 d, or 7 d CORT in the drinking water, examined behavioral impacts with light/dark box, elevated plus maze, operant chamber, and open field tests, measured the effects of CORT on VTA dopamine neuronal activity using patch-clamp electrophysiology and dopamine concentration using fast-scan cyclic voltammetry, and tested the effects of dopamine D2 receptor (D2R) blockade by intra-VTA infusion of a D2R antagonist. CORT treatment induced anxiety-like behavior as well as decreased food-seeking behaviors. We show that chronic CORT treatment decreased excitability and excitatory synaptic transmission onto VTA dopamine neurons. Furthermore, chronic CORT increased somatodendritic dopamine concentration. The D2R antagonist sulpiride restored decreased excitatory transmission and excitability of VTA dopamine neurons. Furthermore, sulpiride decreased anxiety-like behavior and rescued food-seeking behavior in mice with chronic CORT exposure. Together, 7 d CORT treatment induces anxiety-like behavior and impairs food-seeking in a mildly aversive environment. D2R signaling in the VTA might be a potential target to ameliorate chronic CORT-induced anxiety and reward-seeking deficits.SIGNIFICANCE STATEMENT With widespread anti-inflammatory effects throughout the body, corticosteroids (CORT) have been used in a variety of therapeutic conditions. However, long-term CORT treatment causes cognitive impairments and neuropsychiatric disorders. The impact of chronic CORT on the mesolimbic system has not been elucidated. Here, we demonstrate that 7 d CORT treatment increases anxiety-like behavior and attenuates food-seeking behavior in a mildly aversive environment. By elevating local dopamine concentration in the VTA, a region important for driving motivated behavior, CORT treatment suppresses excitability and synaptic transmission onto VTA dopamine neurons. Intriguingly, blockade of D2 receptor signaling in the VTA restores neuronal excitability and food-seeking and alleviates anxiety-like behaviors. Our findings provide a potential therapeutic target for CORT-induced reward deficits.

COMPARING COORDINATED RESPONDING IN PAIRS OF RATS WHEN BOTH OPERANTS AND AGGREGATE PRODUCTS ARE SELECTED BY INTERMITTENT TEMPORAL CONSEQUENCES

Three pairs of rats worked in two adjacent operant chambers separated by a Plexiglas wall. In some experimental conditions, lever-presses were independent operants maintained by either a fixed-interval (FI) or variable interval (VI) schedule. In other conditions, each rat lever- press was part of two interlocked behavior contingencies as part of a metacontingency: its aggregate product, a brief flash of light, was maintained either by a FI or a VI schedule of mutual water presentation. The results clearly show that the interlocking of behavioral contingencies in the design of an experimental metacontingency established a pattern of cooperation between the rats.

Aversion-resistant fentanyl self-administration in mice.

Animal models of compulsive drug use that continues despite negative consequences can be used to investigate the neural mechanisms of addiction. However, models of punished or aversion-resistant opioid self-administration are notably lacking. We sought to develop an aversion-resistant, oral fentanyl self-administration paradigm. In Experiment 1, C57BL/6J male and female, adult mice consumed fentanyl (10μg/mL) in a two-bottle drinking in the dark task and escalating concentrations of quinine were added to the bottles. In Experiment 2, mice were trained to administer oral fentanyl (10μg/mL) in an operant response task. Quinine was next added to the fentanyl solution in escalating concentrations. In Experiment 3, mice were trained to respond for oral fentanyl or fentanyl adulterated with 500μM quinine on every session. In Experiment 4, mice were trained to respond for a 1% sucrose solution before introduction of quinine. Quinine reduced two-bottle choice consumption in males but not in females. Both sexes demonstrated the ability to detect the selected concentrations of quinine in fentanyl. In the operant chamber, mice responded robustly for oral fentanyl but introduction of quinine at any stage of training was insufficient to reduce responding. In contrast, quinine reduced responding for sucrose at concentrations above 250μM. Mice will respond for and consume oral fentanyl in both a two-bottle choice and an operant response task. Quinine is detectable in fentanyl but mice will continue to respond for and consume fentanyl with quinine in both paradigms. These data support the use of these models in behavioral studies of compulsive-like opioid use.

Vibration Source Creation of Unbalance Type with Liquid-Filled Internal Operating Chamber

The creating design features of harmonic vibrations’ submersible source with an internal working chamber, filled with a liquid are considered in the article. The technical requirements for a vibration source operating in a liquid containing mechanical impurities are formulated. Numerical simulation of the unbalance rotation in a liquid are carried. The stationary distribution of fluid pressure on the unbalance blade midsection is calculated under standard conditions and the coefficient of frontal resistance is determined. Calculations were made, taking into account design parameters of source, stresses and deformations of its elements in the process of operation were determined, and the critical frequencies were found. The materials choice for its nodes was substantiated and the advantages in the work of the created source were shown.

Maternal immune activation targeted to a window of parvalbumin interneuron development improves spatial working memory: Implications for autism

Maternal immune activation (MIA) increases risk for neuropsychiatric disorders such as autism spectrum disorder (ASD) in offspring later in life through unknown causal mechanisms. Growing evidence implicates parvalbumin-containing GABAergic interneurons as a key target in rodent MIA models. We targeted a specific neurodevelopmental window of parvalbumin interneurons in a mouse MIA model to examine effects on spatial working memory, a key domain in ASD that can manifest as either impairments or improvements both clinically and in animal models.Pregnant dams received three consecutive intraperitoneal injections of Polyinosinic:polycytidylic acid (poly(I:C), 5 mg/kg) at gestational days 13, 14 and 15. Spatial working memory was assessed in young adult offspring using touchscreen operant chambers and the Trial-Unique Non-matching to Location (TUNL) task. Anxiety, novelty seeking and short-term memory were assessed using Elevated Plus Maze (EPM) and Y-maze novelty preference tasks. Fluorescent immunohistochemistry was used to assess hippocampal parvalbumin cell density, intensity and co-expression with perineuronal nets. qPCR was used to assess the expression of putatively implicated gene pathways.MIA targeting a window of parvalbumin interneuron development increased spatial working memory performance on the TUNL touchscreen task which was not influenced by anxiety or novelty seeking behaviour. The model reduced fetal mRNA levels of Gad1 and adult hippocampal mRNA levels of Pvalb and the distribution of low intensity parvalbumin interneurons was altered.We speculate a specific timing window for parvalbumin interneuron development underpins the apparently paradoxical improved spatial working memory phenotype found both across several rodent models of autism and clinically in ASD.

Serotonergic Innervations of the Orbitofrontal and Medial-prefrontal Cortices are Differentially Involved in Visual Discrimination and Reversal Learning in Rats.

Cross-species studies have identified an evolutionarily conserved role for serotonin in flexible behavior including reversal learning. The aim of the current study was to investigate the contribution of serotonin within the orbitofrontal cortex (OFC) and medial prefrontal cortex (mPFC) to visual discrimination and reversal learning. Male Lister Hooded rats were trained to discriminate between a rewarded (A+) and a nonrewarded (B−) visual stimulus to receive sucrose rewards in touchscreen operant chambers. Serotonin was depleted using surgical infusions of 5,7-dihydroxytryptamine (5,7-DHT), either globally by intracebroventricular (i.c.v.) infusions or locally by microinfusions into the OFC or mPFC. Rats that received i.c.v. infusions of 5,7-DHT before initial training were significantly impaired during both visual discrimination and subsequent reversal learning during which the stimulus–reward contingencies were changed (A− vs. B+). Local serotonin depletion from the OFC impaired reversal learning without affecting initial discrimination. After mPFC depletion, rats were unimpaired during reversal learning but slower to respond at the stimuli during all the stages; the mPFC group was also slower to learn during discrimination than the OFC group. These findings extend our understanding of serotonin in cognitive flexibility by revealing differential effects within two subregions of the prefrontal cortex in visual discrimination and reversal learning.

Poor numerical performance of guppies tested in a Skinner box

We tested the hypothesis that part of the gap in numerical competence between fish and warm-blooded vertebrates might be related to the more efficient procedures (e.g. automated conditioning chambers) used to investigate the former and could be filled by adopting an adapted version of the Skinner box in fish. We trained guppies in a visual numerosity discrimination task, featuring two difficulty levels (3 vs. 5 and 3 vs. 4) and three conditions of congruency between numerical and non-numerical cues. Unexpectedly, guppies trained with the automated device showed a much worse performance compared to previous investigations employing more “ecological” procedures. Statistical analysis indicated that the guppies overall chose the correct stimulus more often than chance; however, their average accuracy did not exceed 60% correct responses. Learning measured as performance improvement over training was significant only for the stimuli with larger numerical difference. Additionally, the target numerosity was selected more often than chance level only for the set of stimuli in which area and number were fully congruent. Re-analysis of prior studies indicate that the gap between training with the Skinner box and with a naturalistic setting was present only for numerical discriminations, but not for colour and shape discriminations. We suggest that applying automated conditioning chambers to fish might increase cognitive load and therefore interfere with achievement of numerosity discriminations.

Individual differences in the nature of conditioned behavior across a conditioned stimulus: Adaptation and application of a model.

Pavlovian conditioning procedures produce marked individual differences in the form of conditioned behavior. For example, when rats are given conditioning trials in which the temporary insertion of a lever into an operant chamber (the conditioned stimulus, CS) is paired with the delivery of food (the unconditioned stimulus, US), they exhibit knowledge of the lever-food relationship in different ways. For some rats (known as sign-trackers), interactions with the lever dominate, while for others (goal-trackers), approaching the food well dominates. A formal model of Pavlovian conditioning (HeiDI) attributes such individual differences in behavior to variations in the perceived salience of the CS and US. An application of the model in which the perceived salience of the CS declines (i.e., adapts) across its duration predicts changes in these individual differences within the presentation of the CS: The sign-tracking bias is predicted to decline and goal-tracking bias is predicted to increase across the presentation of a lever. The accuracy of these predictions was confirmed through analysis of archival data from female and male rats. (PsycInfo Database Record (c) 2020 APA, all rights reserved).