nosepoke

Drug addiction represents a multifaceted and recurrent brain disorder that possesses the capability to create persistent and ineradicable pathological memory. Deep brain stimulation (DBS) has shown a therapeutic potential for neuropsychological disorders, while the precise stimulation targets and therapeutic parameters for addiction remain deficient. Among the crucial brain regions implicated in drug addiction, the dorsal raphe nucleus (DRN) has been found to exert an essential role in the manifestation of addiction memory...

Synthetic exendin-4 (EX4, exenatide), is a GLP-1 receptor agonist used clinically to treat glycemia in Type-2 diabetes mellitus. EX4 also promotes weight loss and alters food reward-seeking behaviors in part due to activation of GLP-1 receptors in the mesolimbic dopamine system. Evidence suggests that GLP-1 receptor activity can directly attenuate cue-induced reward seeking. Here, we tested the effects of EX4 (0.6, 1.2, and 2.4 μg/kg, i.p.) on incentive cue (IC) responding, using a task where rats emit a nosepoke response during an intermittent reward-predictive IC to obtain a sucrose reward...

Increased reinforcer motivation in rats has been repeatedly demonstrated following intermittent-access (IntA) training, where the reinforcer is only available for brief periods during a session, compared to continuous-access (ContA) training where the reinforcer is available throughout the session. The present study investigated whether different associations learned during training on the two procedures contributes to the effect. Two experiments tested the importance of the stimulus-response (S-R) and stimulus-outcome (S-O) associations between the IntA availability cues and the training response and reinforcer, respectively...

To survive, animals must meet their biological needs while simultaneously avoiding danger. However, the neurobiological basis of appetitive and aversive survival behaviors has historically been studied using separate behavioral tasks. While recent studies in mice have quantified appetitive and aversive conditioned responses simultaneously (Heinz et al., 2017; Jikomes et al., 2016), these tasks required different behavioral responses to each stimulus. As many brain regions involved in survival behavior process stimuli of opposite valence, we developed a paradigm in which mice perform the same response (nosepoke) to distinct auditory cues to obtain a rewarding outcome (palatable food) or avoid an aversive outcome (mild footshoock)...

BACKGROUND: Pain in early life may impact on development and risk of chronic pain. We developed an optogenetic Cre/loxP mouse model of "early-life-pain" (ELP) using mice with transgenic expression of channelrhodopsin-2 (ChR2) under control of the Advillin (Avil) promoter, which drives expression of transgenes predominantly in isolectin B4 positive non-peptidergic nociceptors in postnatal mice. Avil-ChR2 (Cre +) and ChR2-flfl control mice were exposed to blue light in a chamber once daily from P1-P5 together with their Cre-negative mother...

UNLABELLED: To survive, animals must meet their biological needs while simultaneously avoiding danger. However, the neurobiological basis of appetitive and aversive survival behaviors has historically been studied using separate behavioral tasks. While recent studies in mice have quantified appetitive and aversive conditioned responses simultaneously (Heinz et al., 2017; Jikomes et al., 2016), these tasks required different behavioral responses to each stimulus. As many brain regions involved in survival behavior process stimuli of opposite valence, we developed a paradigm in which mice perform the same response (nosepoke) to distinct auditory cues to obtain a rewarding outcome (palatable food) or avoid an aversive outcome (mild footshoock)...

When facing a choice, most animals quit drugs in favour of a variety of nondrug alternatives. We recently found, rather unexpectedly, that choice of the nondrug alternative is in fact inflexible and habitual. One possible contributing factor to habitual choice is the intermittency and uncontrollability of choice trials in previous studies. Here, we asked whether and to what extent volitional control over the occurrence of choice trials could change animals' preference by preventing habitual choice. To do so, rats were trained to nosepoke in a hole to trigger the presentation of two operant levers: one associated with cocaine, the other with saccharin...

The study identifies the critical period of early ontogeny, during which social factors have the greatest influence on the operant behavior with positive reinforcement in adult WAG/Rij rats. Individual social isolation of rats from dam and siblings was performed daily for 3 h during postnatal day (PND) 2-8, 9-15, and 16-22. General activity and water consumption were examined using the IntelliCage (IC) in adulthood. The operant behavior training was performed in four consecutive sessions: free exploration of the IC environment (adaptation), learning to retrieve water by nosepoking (nosepoke adaptation), spatial learning to retrieve water in the specific corner (place learning), and retraining with a change of a place preference (reversal learning)...

Drug-associated stimuli take on conditioned reinforcing properties that promote drug-seeking and relapse. Previously, we have demonstrated that daily systemic injections of SNC80 (delta opioid receptor agonist) resulted in dose-dependent increases in responding for the opioid-associated stimulus. In the current experiment, we assessed the extent to which activating and/or blocking delta opioid receptors via a systemic injection of SNC80 or naltrindole, respectively, modified the conditioned reinforcing properties of an opioid-associated stimulus...

While significant effort has been made to understand the neural basis of addiction, it remains unclear exactly how the brain controls motivated behaviors and how drugs of abuse alter these neural systems to control drug taking and seeking. The goal of this study was to understand how cocaine and associated stimuli are encoded in the brain and how neuronal activation in response to cocaine acts to drive drug seeking. In a given brain region, only a small percentage of cells are activated to any stimulus - termed an "ensemble"...

From the preference of one good over another, the strength of the preference cannot automatically be inferred. While money is the common denominator to assess the value of goods in humans, it appears difficult at first glance to put a price tag on the decisions of laboratory animals. Here we used consumer demand tests to measure how much work female mice expend to obtain access to different liquids. The mice could each choose between two liquids, one of which was free. The amount of work required to access the other liquid, by contrast, increased daily...

The goal of our laboratory is to study the mechanisms that promote nicotine use, particularly in vulnerable populations. To more closely mimic human use patterns, the present study employed nicotine vapor methods involving passive exposure for 14 days in adolescent and adult female and male rats. Age and sex differences in approach behavior (nosepokes) were assessed in a port that delivered nicotine plumes on Day 1 and 14 of our exposure regimen. Controls received ambient air in exposure chambers. After the final session, rats received a nicotinic receptor antagonist to precipitate withdrawal...

Trehalose, a sugar from fungi, mimics starvation due to a block of glucose transport and induces Transcription Factor EB- mediated autophagy, likely supported by the upregulation of progranulin. The pro-autophagy effects help to remove pathological proteins and thereby prevent neurodegenerative diseases such as Alzheimer's disease. Enhancing autophagy also contributes to the resolution of neuropathic pain in mice. Therefore, we here assessed the effects of continuous trehalose administration via drinking water using the mouse Spared Nerve Injury model of neuropathic pain...

Strain differences in visual abilities and exploratory tendencies can confound rats' performance in cognitive tests of learning and memory. In the present study we compared the performance of albino Wistar and pigmented Lister Hooded rats in appetitive conditioning and recognition memory procedures, specifically within-subjects inhibitory learning (A+/AX-) and novel object recognition (NOR) variants. The inhibition task included an excitatory training stage and summation and retardation tests. Difference scores were used to help control for individual variation in baseline nosepoke responding...

Drug addiction is considered maladaptive learning, and drug-related memories aroused by the presence of drug related stimuli (drug context or drug-associated cues) promote recurring craving and reinstatement of drug seeking. The mammalian target of rapamycin signaling pathway is involved in reconsolidation of drug memories in conditioned place preference and alcohol self-administration (SA) paradigms. Here, we explored the effect of mTOR inhibition on reconsolidation of addiction memory using cocaine self-administration paradigm...

AIMS: Recently we developed a model to study alcohol-seeking behaviour after withdrawal in a social context in female mice. The model raised several questions that we were eager to address to improve methodology. METHODS: In our model, female mice were group-housed in automated cages with three conditioned (CS+) corners and water in both sides of one separate non-conditioned corner. Water was available with opened doors at all the time of training. We established conditioning by pairing alcohol drinking with light cues...

Divided attention may be more important than ever to comprehend, given ubiquitous distractors in modern living. In humans, concern has been expressed about the negative impact of distraction in education, the home, and the workplace. While acetylcholine supports divided attention, in part via muscarinic receptors, little is known about the specific muscarinic subtypes that may contribute. We designed a novel, high-response rate test of auditory sustained attention, in which rats complete variable-ratio runs on one of two levers, rather than emitting a single response...

Operant behavior procedures often rely on visual stimuli to cue the initiation or secession of a response, and to provide a means for discriminating between two or more simultaneously available responses. While primate and human studies typically use LCD or OLED monitors and touch screens, rodent studies use a variety of methods to present visual cues ranging from traditional incandescent light bulbs, single LEDs, and, more recently, touch screen monitors. Commercially available systems for visual stimulus presentation are costly, challenging to customize, and are typically closed source...

Major depressive disorder is a significant and costly cause of global disability. Until the discovery of the rapid acting antidepressant (RAAD) effects of ketamine, treatments were limited to drugs that have delayed clinical benefits. The mechanism of action of ketamine is currently unclear but one hypothesis is that it may involve neuropsychological effects mediated through modulation of affective biases (where cognitive processes such as learning and memory and decision-making are modified by emotional state)...

Individuals with autism spectrum disorder (ASD) display dysfunction in learning from environmental stimulus that have positive or negative emotional values, posing obstacles to their everyday life. Unfortunately, mechanisms of the dysfunction are still unclear. Although early intervention for ASD victims based on reinforcement learning are commonly used, the mechanisms and characteristics of the improvement are also unknown. By using a mice model of ASD produced by prenatal exposure to valproic acid (VPA), the present work discovered a delayed response-reinforcer forming, and an impaired habit forming in a negative reinforcement learning paradigm in VPA exposure male offspring...