Assessment of impulsivity using an automated, self-adjusting delay discounting procedure.

Modelling delay discounting behavior in rodents is important for understanding the neurobiological mechanisms underlying cognitive control and associated impulsivity disorders. Conventional rodent delay discounting procedures require extensive training and frequent experimenter interaction, as rodents are tested in separate operant chambers away from their home cage. To address these limitations, we adapted and characterize here a self-adjusting delay discounting procedure to an automated CombiCage setup.

Prefrontal Cortical to Mediodorsal Thalamus Projection Neurons Regulate Posterror Adaptive Control of Behavior.

Adaptive control is the online adjustment of behavior to guide and optimize responses after errors or conflict. The neural circuits involved in monitoring and adapting behavioral performance following error are poorly understood. The prefrontal cortex (PFC) plays a critical role in this form of control.

Neural basis of operant behaviors maintained on the differential-reinforcement-of-low-rate (DRL) schedule in rodents.

Various schedules of reinforcement have long been used in experimental psychology to establish and maintain operant behaviors. These reinforcement contingencies have also been widely applied in preclinical psycho- and neurobiology research. However, the differential reinforcement of low-rate response (DRL) schedule has received less attention than other schedules based on response ratios or different types of intervals.

Prenatal exposure to morphine impairs attention and impulsivity in adult rats.

Rationale: An alarming number of neonates born with prenatal exposure to morphine has resulted from the opioid epidemic; however, the long-term effects of prenatal opioid exposure on offspring behavior remain relatively unknown. In this study, we evaluated whether prenatal exposure to the mu opioid receptor agonist, morphine, has enduring effects on cognitive functions in adult life.

Methods: On embryonic days 11-18 (E11-E18), female pregnant rats were injected subcutaneously with either morphine or saline twice daily.

Where Dopaminergic and Cholinergic Systems Interact: A Gateway for Tuning Neurodegenerative Disorders.

Historically, many investigations into neurodegenerative diseases have focused on alterations in specific neuronal populations such as, for example, the loss of midbrain dopaminergic neurons in Parkinson's disease (PD) and loss of cholinergic transmission in Alzheimer's disease (AD). However, it has become increasingly clear that mammalian brain activities, from executive and motor functioning to memory and emotional responses, are strictly regulated by the integrity of multiple interdependent neuronal circuits. Among subcortical structures, the dopaminergic nigrostriatal and mesolimbic pathways as well as cholinergic innervation from basal forebrain and brainstem, play pivotal roles in orchestrating cognitive and non-cognitive symptoms in PD and AD.

Bi-directional regulation of cognitive control by distinct prefrontal cortical output neurons to thalamus and striatum.

The medial prefrontal cortex (mPFC) steers goal-directed actions and withholds inappropriate behavior. Dorsal and ventral mPFC (dmPFC/vmPFC) circuits have distinct roles in cognitive control, but underlying mechanisms are poorly understood. Here we use neuroanatomical tracing techniques, in vitro electrophysiology, chemogenetics and fiber photometry in rats engaged in a 5-choice serial reaction time task to characterize dmPFC and vmPFC outputs to distinct thalamic and striatal subdomains.

Tracing goes viral: Viruses that introduce expression of fluorescent proteins in chemically-specific neurons.

Over the last century, there has been great progress in understanding how the brain works. In particular, the last two decades have been crucial in gaining more awareness over the complex functioning of neurotransmitter systems. The use of viral vectors in neuroscience has been pivotal for such development.

Prefrontal Cortical Projection Neurons Targeting Dorsomedial Striatum Control Behavioral Inhibition.

A neural pathway from prefrontal cortex (PFC) to dorsal striatum (DS) has been suggested to mediate cognitive control of behavior, including proactive inhibitory control and attention. However, a direct causal demonstration thereof is lacking. Here, we show that selective chemogenetic silencing of corticostriatal PFC neurons in rats increases premature responses.

Personality driven alcohol and drug abuse: New mechanisms revealed.

While the majority of the regular consumers of alcohol controls their consumption well over life span and even takes instrumentalization benefits from it, a minority, but yet high total number of users develops an alcohol addiction. It has long been known that particular personality types are more addiction prone than others. Here we review recent progress in the understanding of neurobiological pathways that determine personality and facilitate drug abuse.

The Neuropharmacology of Impulsive Behaviour, an Update.

Neuropharmacological interventions in preclinical translational models of impulsivity have tremendously contributed to a better understanding of the neurochemistry and neural basis of impulsive behaviour. In this regard, much progress has been made over the last years, also due to the introduction of novel techniques in behavioural neuroscience such as optogenetics and chemogenetics. In this chapter, we will provide an update of how the behavioural pharmacology field has progressed and built upon existing data since an earlier review we wrote in 2008.

The role of impulsivity as predisposing behavioural trait in different aspects of alcohol self-administration in rats.

Background: Therapeutic interventions to promote abstinence and prevent relapse in alcohol use disorder (AUD) are limitedly available. Therefore, targeting risk factors in the onset and maintenance of AUD could pose an interesting alternative treatment strategy. In this regard, over the last decade trait impulsivity has received considerable attention as such a risk factor predisposing substance dependence both in clinical populations and preclinical rodent studies.

An automated home-cage-based 5-choice serial reaction time task for rapid assessment of attention and impulsivity in rats.

Rationale: The 5-choice serial reaction time task (5-CSRTT) is a widely used operant task for measuring attention and motor impulsivity in rodents. Training animals in this task requires an extensive period of daily operant sessions. Recently, a self-paced, automated version of this task has been developed for mice, which substantially reduces training time.

Optogenetic and chemogenetic approaches to manipulate attention, impulsivity and behavioural flexibility in rodents.

Studies manipulating neural activity acutely with optogenetic or chemogenetic intervention in behaving rodents have increased considerably in recent years. More often, these circuit-level neural manipulations are tested within an existing framework of behavioural testing that strives to model complex executive functions or symptomologies relevant to multidimensional psychiatric disorders in humans, such as attentional control deficits, impulsivity or behavioural (in)flexibility. This methods perspective argues in favour of carefully implementing these acute circuit-based approaches to better understand and model cognitive symptomologies or their similar isomorphic animal behaviours, which often arise and persist in overlapping brain circuitries.

Striatal alcohol cue-reactivity is stronger in male than female problem drinkers.

Despite apparent sex differences in the development and treatment of alcohol use disorder, relatively little is known about the underlying neural mechanisms. In this study, we therefore investigated neural cue-reactivity in a sample of male (n = 28) and female (n = 27) problem drinkers (matched on age and alcohol use severity) with an average alcohol use disorder identification test score of 12 which is indicative of a likely alcohol use disorder. Neural cue-reactivity data were extracted from four regions of interest: the ventral and dorsal striatum and the ventral and dorsal anterior cingulate cortex, with a significance level set at p < 0.

Examination of the effects of cannabinoid ligands on decision making in a rat gambling task.

Although exposure to delta-9-tetrahydrocannabinol (THC) is perceived to be relatively harmless, mounting evidence has begun to show that it is associated with a variety of cognitive deficits, including poor decision making. THC-induced impairments in decision making are thought to be the result of cannabinoid CB1 receptor activation, and although clinical literature suggests that chronic activation via THC contributes to perturbations in decision making, acute CB1 receptor modulation has yielded mixed results. Using an animal model to examine how CB1-specific ligands impact choice biases would provide significant insight as to how recruitment of the endocannabinoid system may influence decision making.

A high working memory load prior to memory retrieval reduces craving in non-treatment seeking problem drinkers.

Background: Reconsolidation-based interventions have been suggested to be a promising treatment strategy for substance use disorders. In this study, we aimed to investigate the effectiveness of a working memory intervention to interfere with the reconsolidation of alcohol-related memories in a sample of non-treatment seeking heavy drinkers.

Methods: Participants were randomized to one of the two conditions that underwent a 3-day intervention: in the experimental condition, a 30-min working memory training was performed immediately after a 15-min memory retrieval session (i.

Dissociable effects of cocaine and yohimbine on impulsive action and relapse to cocaine seeking.

Rationale: A strong association has been demonstrated between various forms of impulsivity and addiction-like behavior in both humans and rats.

Objectives: In this study, we investigated how impulsive action, as measured in the 5-choice serial reaction time task (5-CSRTT), is affected during various stages of cocaine taking and seeking and by relapse-provoking stimuli in animals that were trained both in an intravenous cocaine self-administration paradigm and in the 5-CSRTT.

Methods: Rats were concurrently trained in the 5-CSRTT and cocaine self-administration protocol, and subsequently, the effects of cocaine (7.

Deep brain stimulation of the nucleus accumbens core but not shell reduces motivational components of heroin taking and seeking in rats.

Background: Deep brain stimulation is explored as a new intervention for treatment-resistant substance use dependence. A candidate brain region is the nucleus accumbens, due to its involvement in reward and motivation. This study aimed to explore effects of NAcore and NAshell deep brain stimulation on aspects of heroin taking and seeking in a self-administration model for rats.

Deep Brain Stimulation of the Nucleus Accumbens Core Affects Trait Impulsivity in a Baseline-Dependent Manner.

Deep brain stimulation (DBS) of the nucleus accumbens (NA) is explored as a treatment for refractory psychiatric disorders, such as obsessive-compulsive disorder (OCD), depressive disorder (MDD), and substance use disorder (SUD). A common feature of some of these disorders is pathological impulsivity. Here, the effects of NAcore DBS on impulsive choice and impulsive action, two distinct forms of impulsive behavior, were investigated in translational animal tasks, the delayed reward task (DRT) and five-choice serial reaction time task (5-CSRTT), respectively.

Sustained Attentional States Require Distinct Temporal Involvement of the Dorsal and Ventral Medial Prefrontal Cortex.

Attending the sensory environment for cue detection is a cognitive operation that occurs on a time scale of seconds. The dorsal and ventral medial prefrontal cortex (mPFC) contribute to separate aspects of attentional processing. Pyramidal neurons in different parts of the mPFC are active during cognitive behavior, yet whether this activity is causally underlying attentional processing is not known.

Prefrontal cortical neuregulin-ErbB modulation of inhibitory control in rats.

Impulse control disturbances are key features of various neuropsychiatric and neurological disorders, such as attention-deficit/hyperactivity disorder, drug addiction, Parkinson disease and schizophrenia. Whereas over the last years accumulating evidence has highlighted monoaminergic modulation of the processes underlying impulse control, investigating novel mechanisms beyond monoamines may provide new intervention strategies to ameliorate impulse control disturbances. Recent work has associated the neuregulin (Nrg)-ErbB pathway with several neuropsychiatric diseases, as well as indicated its involvement in murine measures of impulse control.

Compulsivity in obsessive-compulsive disorder and addictions.

Compulsive behaviors are driven by repetitive urges and typically involve the experience of limited voluntary control over these urges, a diminished ability to delay or inhibit these behaviors, and a tendency to perform repetitive acts in a habitual or stereotyped manner. Compulsivity is not only a central characteristic of obsessive-compulsive disorder (OCD) but is also crucial to addiction. Based on this analogy, OCD has been proposed to be part of the concept of behavioral addiction along with other non-drug-related disorders that share compulsivity, such as pathological gambling, skin-picking, trichotillomania and compulsive eating.