nosepoke

BACKGROUND: Cholinergic interneurons (ChINs) in the nucleus accumbens (NAc) play critical roles in processing information related to reward. However, the contribution of ChINs to the emergence of addiction-like behaviors and its underlying molecular mechanisms remain elusive. METHODS: We employed cocaine self-administration to identify two mouse subpopulations: susceptible and resilient to cocaine seeking. We compared the subpopulations for physiological responses with single-unit recording of NAc ChINs, and for gene expression levels with RNA sequencing of ChINs sorted using fluorescence-activated cell sorting...

BACKGROUND: Binge-eating disorder is a pervasive addiction-like disorder that is defined by excessive and uncontrollable consumption of food within brief periods of time. The aim of the current study was to examine the role of the brain noradrenergic system in binge-like eating through the use of the alpha-1 adrenergic receptor antagonist prazosin. METHODS: For this purpose, we employed a limited access model whereby male Wistar rats were allowed to nosepoke for either chow ( Chow rats) or a sugary, highly palatable food ( Palatable rats) for 1 h/day...

Recent trends in cannabis legalization have increased the necessity to better understand the effects of cannabis use. Animal models involving traditional cannabinoid self-administration approaches have been notoriously difficult to establish and differences in the drug used and its route of administration have limited the translational value of preclinical studies. To address this challenge in the field, we have developed a novel method of cannabis self-administration using response-contingent delivery of vaporized Δ9 -tetrahydrocannabinol-rich (CANTHC ) or cannabidiol-rich (CANCBD ) whole-plant cannabis extracts...

CB1 receptor antagonists disrupt operant responding for food and drug reinforcers, and cue-induced reinstatement of cocaine and heroin seeking. Conversely, enhancing endocannabinoid signaling, particularly 2-arachidonyl glycerol (2-AG), by inhibition of monoacyl glycerol lipase (MAGL), may facilitate some aspects of reward seeking. To determine how endocannabinoid signaling affects responding to reward-predictive cues, we employed an operant task that allows us to parse the incentive motivational properties of cues...

Fragile X syndrome (FXS) is the leading cause of inherited intellectual disability and a significant genetic contributor to Autism spectrum disorder. In addition to autistic-like phenotypes, individuals with FXS are subject to developing numerous comorbidities, one of the most prevalent being seizures. In the present study, we investigated how a single early-life seizure superimposed on a genetic condition impacts the autistic-like behavioral phenotype of the mouse. We induced status epilepticus (SE) on postnatal day (PD) 10 in Fmr1 wild type (WT) and knockout (KO) mice...

A recent push to provide more translationally relevant preclinical models for examination of pharmacological mechanisms underlying inhaled substances of abuse has resulted in the development of equipment and methods that allows exposure of freely moving rodents to aerosolized psychoactive drugs. In the present study, synthetic cannabinoids (CP55,940, AB-CHMINACA, and AMB-FUBINACA) were administered intraperitoneally (i.p.) or aerosolized via a modified electronic cigarette device. Subsequently, the compounds were evaluated in adult male and female C57/Bl6 mice trained to discriminate i...

Inflammation or injuries of the trigeminal nerve are often associated with persistent facial pain and its sequelae. A number of models have been described to study trigeminal pain in rodents, but the long-lasting behavioral consequences are unknown. This study characterizes the impact of a distal infraorbital nerve injury, called DIONI, which consists of ligature and transection of distal fibers of the infraorbital nerve. We assessed nociception using a conflict paradigm and optogenetics, and a set of reward, aversion, spatial, temporal, and competition tasks in the IntelliCage to study multiple aspects of cognition, circadian rhythms, and social interactions in groups of mice in home cage environments...

The orbitofrontal cortex (OFC) and the medial prefrontal cortex (mPFC) are known to participate in risk-based decision-making. However, whether neuronal activities of these two brain regions play similar or differential roles during different stages of risk-based decision-making process remains unknown. Here we conducted multi-channel in vivo recordings in the OFC and mPFC simultaneously when rats were performing a gambling task. Rats were trained to update strategy as the task was shifted in two stages. Behavioral testing suggests that rats exhibited different risk preferences and response latencies to food rewards during stage-1 and stage-2...

AIM: Attention-deficit/hyperactivity disorder is a heterogeneous neurobiological disorder that is characterized by inattention, impulsivity, and an increase in motor activity. Although methylphenidate has been used as a medication for decades, unknown is whether methylphenidate treatment can cause drug dependence in patients with attention-deficit/hyperactivity disorder. This study investigated the reward-enhancing effects of methylphenidate using intracranial self-stimulation in an animal model of attention-deficit/hyperactivity disorder, dopamine transporter knockout mice...

Rodent models have been especially useful for investigating adolescent ethanol exposure. However, there is a paucity of studies examining sex differences in behavioral intoxication from adolescent ethanol drinking. Here, we used an ethanol drinking model to investigate if adolescent rats of both sexes readily drink ethanol to measurable behavioral intoxication, indicated by increased impulsive action and motor incoordination. Beginning on postnatal day (P) 28, male and female Long-Evans rats were given 30-min access to a solution of sucrose (20%) or sweetened ethanol (20% sucrose +15% ethanol) every other day until P60 and once after 2 weeks of forced abstinence (on P75)...

It is about half a century ago when the so-called "Wise model" to study alcohol drinking behavior in rats was established. The model was based on voluntary intermittent access to increasing concentrations of alcohol. We aimed to establish a model of alcohol craving and used an extinction test on withdrawal days 1 and 10 to study motivation for alcohol. For this purpose, the alcohol drinking training was paired with light cues to establish conditioning. The extinction test was carried out without alcohol but in the presence of light cues and empty bottles...

Mesolimbic dopamine perturbations modulate performance of reward-seeking behavior, with tasks requiring high effort being especially vulnerable to disruption of dopamine signaling. Previous work primarily investigated long-term perturbations such as receptor antagonism and dopamine depletion, which constrain the ability to assess dopamine contributions to effort expenditure in isolation from other behavior events, such as reward consumption. Also unclear is if dopamine is required for both initiation and maintenance when a sequence of multiple instrumental responses is required...

Automated homecage monitoring systems are now widely recognized and used tools in cognitive neuroscience. However, few of these studies cover pharmacological interventions. Scopolamine, an anticholinergic memory disrupting agent is frequently used to study learning behavior. We studied the impact of scopolamine treatment in a relevant dose-range on activity, drinking behavior and reversal learning of C57BL/DJ mice in a homecage-like, social environment, using the IntelliCage. Naïve mice were first habituated to the IntelliCage, where they learned to nosepoke in any of the four corners in order to gain access to the water reward...

Decision making refers to the process that subjects use to choose between competing courses of action based on the expected costs and benefits of their consequences. However, few studies have addressed the neuronal mechanisms behind the processes of how costs and benefits influence decision making. Here we investigated the neuronal representation of costs and benefits towards a goal-directed action under a differential reward schedule by training rats to perform a "Do more, get more" (DM-GM) task utilizing a nosepoke operandum, where longer nosepoke durations resulted in correspondingly larger rewards...

Opioid misuse is at historically high levels in the United States, with inhalation (ie, smoking and vaping) being one of the most common routes of consumption. We developed and validated a novel preclinical model of opioid self-administration by inhalation that does not require surgery and reliably produces somatic and motivational signs of dependence. Rats were trained to perform an operant response (nosepoke) to receive 10 s of vaporized sufentanil, a potent opioid, in 2 h daily sessions. Rats readily and concentration-dependently self-administered vaporized sufentanil...

Addiction is often characterized by intense motivation for a drug, which may be narrowly focused at the expense of other rewards. Here, we examined the role of amygdala-related circuitry in the amplification and narrowing of motivation focus for intravenous cocaine. We paired optogenetic channelrhodopsin (ChR2) stimulation in either central nucleus of amygdala (CeA) or basolateral amygdala (BLA) of female rats with one particular nose-poke porthole option for earning cocaine infusions (0.3 mg/kg, i.v.). A second alternative porthole earned identical cocaine but without ChR2 stimulation...

A series of experiments illustrated the effectiveness and flexibility of a newly developed Automated Remote Environmental Navigation Apparatus (ARENA) as an alternative to traditional operant and open-field procedures. This system improves the concept developed by Badelt and Blaisdell (Behavior Research Methods, 40, 613-621, 2008; see also Leising, Garlick, Parenteau, & Blaisdell in Behavioural Processes, 81, 105-113, 2009), with significant upgrades in flexibility and reliability, as well as a reduction in cost...

RATIONALE: A major issue in the addiction field is the limited number of animal models of the voluntary induction and maintenance of alcohol dependence in outbred rats. OBJECTIVES: To address this issue, we developed a novel apparatus that vaporizes alcohol for 2-10 min after an active nosepoke response. METHODS: Male Wistar rats were allowed to self-administer alcohol vapor for 8 h/day every other day for 24 sessions (escalated) or eight sessions (non-escalated)...

Left-right (L-R) asymmetry is a fundamental feature of brain function, but the mechanisms underlying functional asymmetry remain largely unknown. We previously identified structural and functional asymmetries in the circuitry of the mouse hippocampus that result from the asymmetrical distribution of NMDA receptor GluR ε2 (NR2B) subunits. By examining the synaptic distribution of ε2 subunits, we found that β2-microglobulin (β2m)-deficient mice that are defective in the stable cell surface expression of major histocompatibility complex class I (MHCI) lack this circuit asymmetry...

The anterior cingulate cortex (ACC) is crucial for decision making which involves the processing of cost-benefit information. Our previous study has shown that ACC is essential for self-paced decision making. However, it is unclear how ACC neurons represent cost-benefit selections during the decision-making process. In the present study, we trained rats on the same "Do More Get More" (DMGM) task as in our previous work. In each trial, the animals stand upright and perform a sustained nosepoke of their own will to earn a water reward, with the amount of reward positively correlated to the duration of the nosepoke (i...