Caleb J Browne

Caleb J Browne
Icahn School of Medicine at Mount Sinai | MSSM · Department of Neuroscience

PhD

About

32
Publications
3,257
Reads
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373
Citations
Additional affiliations
October 2017 - present
Icahn School of Medicine at Mount Sinai
Position
  • PostDoc Position
May 2016 - July 2016
University of Toronto
Position
  • Instructor
September 2012 - July 2017
University of Toronto
Position
  • PhD, Psychology

Publications

Publications (32)
Article
Acute pharmacological elevations of serotonin (5-hydroxytryptamine; 5-HT) activity decrease operant responding for primary reinforcers, suggesting that 5-HT reduces incentive motivation. The mechanism by which 5-HT alters incentive motivation is unknown, but parallel evidence that 5-HT2C receptor agonists also reduce responding for primary reinforc...
Article
Converging lines of behavioral, electrophysiological, and biochemical evidence suggest that 5-HT2C receptor signaling may bidirectionally influence reward-related behavior through an interaction with the mesolimbic dopamine (DA) system. Here we directly test this hypothesis by examining how modulating 5-HT2C receptor activity affects DA-dependent b...
Article
Full-text available
The monoamine neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) exerts an inhibitory influence over motivation, but the circuits mediating this are unknown. Here, we used an optogenetic approach to isolate the contribution of dorsal raphe nucleus (DRN) 5-HT neurons and 5-HT innervation of the mesolimbic dopamine (DA) system to motivated behavi...
Article
Depression and substance use disorders are often comorbid, but the reasons for this are unclear. In human studies, it is difficult to determine how one disorder may affect predisposition to the other and what the underlying mechanisms might be. Instead, animal studies allow experimental induction of behaviors relevant to depression and drug-taking,...
Article
Opioid use kills tens of thousands of Americans each year, devastates families and entire communities, and cripples the health care system. Exposure to opioids causes long-term changes to brain regions involved in reward processing and motivation, leading vulnerable individuals to engage in pathological drug seeking and drug taking that can remain...
Preprint
The ability of neurons to respond to external stimuli involves adaptations of gene expression. The transcription factor, ΔFOSB, is important for the development of drug addiction, however, its gene targets have not been identified. Here we use CUT&RUN to map the genome-wide enrichment of ΔFOSB binding in the two major neuronal cell types of the nuc...
Article
Background Over the course of chronic drug use, brain transcriptional neuroadaptation are thought to contribute to a change in drug use behavior over time. The function of the transcription factor CREB within the nucleus accumbens (NAc) has been well documented in opposing the rewarding properties of many classes of drugs, yet the gene targets thro...
Article
Full-text available
Major depressive disorder (MDD) is the leading cause of disability worldwide. There is an urgent need for objective biomarkers to diagnose this highly heterogeneous syndrome, assign treatment, and evaluate treatment response and prognosis. MicroRNAs (miRNAs) are short non-coding RNAs, which are detected in body fluids that have emerged as potential...
Preprint
A hallmark of addiction is the ability of drugs of abuse to trigger relapse after periods of prolonged abstinence. Here, we describe a novel epigenetic mechanism whereby chronic cocaine exposure causes lasting chromatin and downstream transcriptional modifications in the nucleus accumbens (NAc), a critical brain region controlling motivation. We li...
Article
Background Social experiences influence susceptibility to substance use disorder. The adolescent period is associated with the development of social reward and is exceptionally sensitive to disruptions to reward-associated behaviors by social experience. Social isolation during adolescence alters anxiety- and reward-related behaviors in adult males...
Preprint
The complex nature of the transcriptional networks underlying addictive behaviors suggests intricate cooperation between diverse gene regulation mechanisms that go beyond canonical activity-dependent pathways. Here we implicate in this process a novel nuclear receptor transcription factor, Retinoid X Receptor Alpha (RXRα), which we identified bioin...
Preprint
Full-text available
Women suffer from depression at twice the rate of men, but the underlying molecular mechanisms are poorly understood. Here, we identify dramatic baseline sex differences in expression of long noncoding RNAs (lncRNAs) in human postmortem brain tissue that are profoundly lost in depression. One such lncRNA, RP11-298D21.1 (which we termed FEDORA), is...
Article
Paternal stress can induce long-lasting changes in germ cells potentially propagating heritable changes across generations. To date, no studies have investigated differences in transmission patterns between stress-resilient and stress-susceptible mice. We tested the hypothesis that transcriptional alterations in sperm during chronic social defeat s...
Article
Full-text available
Animals susceptible to chronic social defeat stress (CSDS) exhibit depression-related behaviors, with aberrant transcription across several limbic brain regions, most notably in the nucleus accumbens (NAc). Early life stress (ELS) promotes susceptibility to CSDS in adulthood, but associated enduring changes in transcriptional control mechanisms in...
Article
Background Major depressive disorder (MDD) is a pervasive and debilitating syndrome characterized by mood disturbances, anhedonia, and alterations in cognition. While the prevalence of MDD is twice as high for women compared to men, little is known about the molecular mechanisms that drive sex differences in depression susceptibility. Methods We d...
Preprint
Adolescence is a sensitive window for reward- and stress-associated behavior. Although stress during this period causes long-term changes in behavior in males, how females respond is relatively unknown. Here we show that social isolation stress in adolescence, but not adulthood, induces persistent but opposite effects on anxiety- and cocaine-relate...
Article
The nucleus accumbens (NAc) is a critical brain reward region that mediates the rewarding effects of drugs of abuse, including those of morphine and other opiates. Drugs of abuse induce widespread alterations in gene transcription and dendritic spine morphology in medium spiny neurons (MSNs) of the NAc that ultimately influence NAc excitability and...
Article
Rodent studies suggest that dopamine signaling at D2/3 receptors in the ventral striatum is critical for reward motivation. Whether this is also true in humans is unclear. Positron emission tomography studies in healthy humans have generally not observed a relationship between D2/3 receptor availability in the ventral striatum and motivation. We de...
Article
Full-text available
Objectives: These experiments examined the effects of selective 5-HT1A, 5-HT2A and 5-HT2C receptor ligands on responding for a conditioned reinforcer (CRf). Effects of these ligands were measured under basal conditions and following elevated dopamine (DA) activity produced by the DA reuptake inhibitor methylphenidate. Methods: Water-restricted r...
Article
Full-text available
Olfactory processing is thought to be actively modulated by the top-down input from cortical regions, but the behavioural function of these signals remains unclear. Here we find that cortical feedback from the anterior olfactory nucleus pars medialis (mAON) bidirectionally modulates olfactory sensitivity and olfaction-dependent behaviours. To ident...
Article
Full-text available
Rationale Environmental factors influence the etiology of many psychiatric disorders. Likewise, environmental factors can alter processes central to motivation. Therefore, motivational deficits present in many disorders may be influenced by early life environmental conditions. Objective We examined whether housing animals in different environmental...
Article
Pramipexole is a clinically important dopamine receptor agonist with reported selectivity for dopamine D3 receptors over other dopaminergic and non-dopaminergic sites. Many of its behavioural effects are therefore attributed to D3 receptor activity. Here we relate pramipexole's ex vivo D2 and D3 receptor binding (measured using [(3)H]-(+)-PHNO bind...
Article
Characterization of responding for conditioned reinforcement in mice is important to implement genetic tools in examining the neurobiological mechanisms underlying reward-related learning and incentive motivation. Inbred C57BL/6 mice, outbred CD-1 mice, and outbred Sprague-Dawley rats underwent Pavlovian conditioning in which a conditioned stimulus...
Article
Full-text available
Inhalation of vapors from toluene-containing products results in euphoria accompanied by a variety of cognitive impairments and motor dysfunctions. The profound behavioral changes observed during and following toluene inhalation suggest changes in the activity of cells in potentially many brain regions; however, a comprehensive assessment of the ne...

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