Histone deacetylase 5 in prelimbic prefrontal cortex limits context-associated cocaine seeking.

Background: Repeated cocaine use produces neuroadaptations that support drug craving and relapse in substance use disorders (SUDs). Powerful associations formed with drug-use environments can promote a return to active drug use in SUD patients, but the molecular mechanisms that control the formation of these prepotent drug-context associations remain unclear.

Methods: In the rat intravenous cocaine self-administration (SA) model, we examined the role and regulation of histone deacetylase 5 (HDAC5) in the prelimbic (PrL) and infralimbic (IL) cortices in context-associated drug seeking.

The activity-regulated cytoskeleton-associated protein (Arc) functions in a cell type- and sex-specific manner in the adult nucleus accumbens to regulate non-contingent cocaine behaviors.

Repeated cocaine use produces adaptations in brain function that contribute to long-lasting behaviors associated with cocaine use disorder (CUD). In rodents, the activity-regulated cytoskeleton-associated protein (Arc) can regulate glutamatergic synaptic transmission, and cocaine regulates Arc expression and subcellular localization in multiple brain regions, including the nucleus accumbens (NAc)-a brain region linked to CUD-related behavior. We show here that repeated, non-contingent cocaine administration in global Arc KO male mice produced a dramatic hypersensitization of cocaine locomotor responses and drug experience-dependent sensitization of conditioned place preference (CPP).

NPAS4 supports cocaine-conditioned cues in rodents by controlling the cell type-specific activation balance in the nucleus accumbens.

Powerful associations that link drugs of abuse with cues in the drug-paired environment often serve as prepotent relapse triggers. Drug-associated contexts and cues activate ensembles of nucleus accumbens (NAc) neurons, including D1-class medium spiny neurons (MSNs) that typically promote, and D2-class MSNs that typically oppose, drug seeking. We found that in mice, cocaine conditioning upregulated transiently the activity-regulated transcription factor, Neuronal PAS Domain Protein 4 (NPAS4), in a small subset of NAc neurons.

The role of the dorsal striatum in a mouse model for fragile X syndrome: Behavioral and dendritic spine assessment.

Fragile X syndrome (FXS), a leading monogenic cause of autism spectrum disorders (ASDs), typically occurs as the result of a mutation silencing the Fmr1 gene, preventing production of the fragile X messenger ribonucleoprotein (FMRP). FXS is characterized, in part, by hyperactivity, impaired behavioral flexibility, and the development of repetitive, or stereotyped, behaviors. While these phenotypes are influenced by striatal activity, few studies have examined FXS or FMRP in the context of striatal function.

Jugular Vein Catheter Design and Cocaine Self-Administration Using Mice: A Comprehensive Method.

Intravenous self-administration (IVSA) is a behavioral method of voluntary drug intake in animal models which is used to study the reinforcing effects of drugs of abuse. It is considered to have greater face validity in the study of substance use and abuse than other assays, and thus, allows for valuable insight into the neurobiological basis of addiction, and the development of substance abuse disorders. The technique typically involves surgically inserting a catheter into the jugular vein, which enables the infusion of drug solution after the performance of a desired operant behavior.

The fragile X mental retardation protein promotes adjustments in cocaine self-administration that preserve reinforcement level.

The fragile X mental retardation protein (FMRP), an RNA-binding protein, regulates cocaine-induced neuronal plasticity and is critical for the normal development of drug-induced locomotor sensitization, as well as reward-related learning in the conditioned place preference assay. However, it is unknown whether FMRP impacts behaviors that are used to more closely model substance use disorders. Utilizing a cocaine intravenous self-administration (IVSA) assay in Fmr1 knockout (KO) and wild-type (WT) littermate mice, we find that, despite normal acquisition and extinction learning, Fmr1 KO mice fail to make a normal upward shift in responding during dose-response testing.

The Fragile X Mental Retardation Protein Regulates Striatal Medium Spiny Neuron Synapse Density and Dendritic Spine Morphology.

The fragile X mental retardation protein (FMRP), an RNA-binding protein that mediates the transport, stability, and translation of hundreds of brain RNAs, is critically involved in regulating synaptic function. Loss of FMRP, as in fragile X syndrome (FXS), is a leading monogenic cause of autism and results in altered structural and functional synaptic plasticity, widely described in the hippocampus and cortex. Though FXS is associated with hyperactivity, impaired social interaction, and the development of repetitive or stereotyped behaviors, all of which are influenced by striatal activity, few studies have investigated the function of FMRP here.

A single episode of early-life status epilepticus impacts neonatal ultrasonic vocalization behavior in the Fmr1 knockout mouse.

Fragile X syndrome (FXS) is a genetic disorder caused by a trinucleotide (CGG) expansion mutation in the Fmr1 gene located on the X chromosome. It is characterized by hyperactivity, increased anxiety, repetitive-stereotyped behaviors, and impaired language development. Many children diagnosed with FXS also experience seizures during their lifetime.

A single early-life seizure results in long-term behavioral changes in the adult Fmr1 knockout mouse.

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.

Deletion of results in sex-specific changes in behavior.

Objective: In this study, we used a systemic knockout in order to investigate both genotype- and sex-specific differences across multiple measures of sociability, repetitive behaviors, activity levels, anxiety, and fear-related learning and memory.

Background: Fragile X syndrome is the most common monogenic cause of intellectual disability and autism. Few studies to date have examined sex differences in a mouse model of Fragile X syndrome, though clinical data support the idea of differences in both overall prevalence and phenotype between the sexes.

Early-life status epilepticus acutely impacts select quantitative and qualitative features of neonatal vocalization behavior: Spectrographic and temporal characterizations in C57BL/6 mice.

Early-life seizures are known to cause long-term deficits in social behavior, learning, and memory, however little is known regarding their acute impact. Ultrasonic vocalization (USV) recordings have been developed as a tool for investigating early communicative deficits in mice. Previous investigation from our lab found that postnatal day (PD) 10 seizures cause male-specific suppression of 50-kHz USVs on PD12 in 129 SvEvTac mouse pups.