About

Brandon Warren, Ph.D., received his B.S., M.S., and Ph.D. from Florida State University and completed a postdoctoral fellowship at the National Institute on Drug Abuse in Baltimore, Maryland. His research integrates behavioral, biochemical, and microscopic approaches to investigate the role of neuronal ensembles—patterns of neurons activated during behavior—in animal models of drug addiction. Warren's lab focuses on decoding how drug memories are stored in the brain, hypothesizing that these learned associations are encoded by sparsely distributed neuronal ensembles that are selected by cues and reinforcers. Using Fos expression to identify neuronal ensembles activated during behavior, his work involves characterizing and manipulating these ensembles with transgenic rat lines to better understand memory encoding related to addiction. His research aims to develop potential treatments for drug addiction by targeting specific memories or drug-related neuronal patterns.

Research topics

• Developmental psychology
• Neuroscience
• Psychology
• Biology
• Clinical psychology
• Communication

Selected publications

• Efficacy Modulation and Structural Insights of Mu Opioid-Sparing Agents (Abstract ID: 231854)

  Journal of Pharmacology and Experimental Therapeutics · 2026-05-01

  article
  PublisherDOI

• Neuronal ensembles formed rapidly in the prelimbic cortex mediate initial and maintained cocaine-seeking behavior in male and female rats

  Neuropharmacology · 2025-09-16 · 1 citations

  articleOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

• Distinct prelimbic cortex ensembles encode response execution and inhibition

  Proceedings of the National Academy of Sciences · 2025-09-08 · 1 citations

  articleOpen access

  Learning when to initiate or withhold actions is essential for survival, requiring the integration of past experiences with new information to adapt to changing environments. The prelimbic cortex (PL) plays a central role in this process, with a stable PL neuronal population (ensemble) recruited during operant reward learning to encode response execution. However, it is unknown how this established reward-learning ensemble adapts to changing reward contingencies, such as reward omission during extinction. Specifically, does the same ensemble adjust its activity to support behavior suppression, or is a distinct ensemble recruited for this new learning? Our data reveal that operant extinction learning recruits a distinct PL Extinction ensemble to support response inhibition, and concerted engagement of both ensembles encodes both ongoing and subsequent context-specific behavior. Using single-cell calcium imaging, we longitudinally tracked PL neurons in rats as they pressed a lever for food rewards (Training), learned to suppress responding upon reward omission (Extinction), and reinstated responding following a noncontingent "priming" pellet (Reinstatement). We trained decoders on individual rats' PL activity patterns to predict trial-wise responses and used an in silico deletion approach to identify separate PL Training and Extinction ensembles associated with response execution and inhibition, respectively. Critically, both ensembles were reengaged and maintained their distinct roles during Reinstatement. These findings highlight ensemble-based encoding of multiple, even opposing, learned associations within the same region, demonstrating how selective ensemble recruitment enables behavioral flexibility under changing contingencies.

  PublisherDOI

• Distinct prelimbic cortex ensembles encode response execution and inhibition

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-02-24

  preprintOpen access

  Abstract Learning when to initiate or withhold actions is essential for survival and requires integration of past experiences with new information to adapt to changing environments. While stable prelimbic cortex (PL) ensembles have been identified during reward learning, it remains unclear how they adapt when contingencies shift. Does the same ensemble adjust its activity to support behavioral suppression upon reward omission, or is a distinct ensemble recruited for this new learning? We used single-cell calcium imaging to longitudinally track PL neurons in rats across operant food reward Training, Extinction and Reinstatement, trained rat-specific decoders to predict trial-wise behavior, and implemented an in-silico deletion approach to characterize ensemble contributions to behavior. We show that operant training and extinction recruit distinct PL ensembles that encode response execution and inhibition, and that both ensembles are re-engaged and maintain their roles during Reinstatement. These findings highlight ensemble-based encoding of multiple learned associations within a region, with selective ensemble recruitment supporting behavioral flexibility under changing contingencies.

  PublisherOA PDFDOI

• Separate gut-brain circuits for fat and sugar reinforcement combine to promote overeating

  Cell Metabolism · 2024-01-18 · 95 citations

  articleOpen access

  Food is a powerful natural reinforcer that guides feeding decisions. The vagus nerve conveys internal sensory information from the gut to the brain about nutritional value; however, the cellular and molecular basis of macronutrient-specific reward circuits is poorly understood. Here, we monitor in vivo calcium dynamics to provide direct evidence of independent vagal sensing pathways for the detection of dietary fats and sugars. Using activity-dependent genetic capture of vagal neurons activated in response to gut infusions of nutrients, we demonstrate the existence of separate gut-brain circuits for fat and sugar sensing that are necessary and sufficient for nutrient-specific reinforcement. Even when controlling for calories, combined activation of fat and sugar circuits increases nigrostriatal dopamine release and overeating compared with fat or sugar alone. This work provides new insights into the complex sensory circuitry that mediates motivated behavior and suggests that a subconscious internal drive to consume obesogenic diets (e.g., those high in both fat and sugar) may impede conscious dieting efforts.

  PublisherDOI

• Self-administration acquisition latency predicts locomotor sensitivity to cocaine in male rats

  Behavioural Brain Research · 2024-07-29

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Nucleus accumbens neuronal ensembles vary with cocaine reinforcement in male and female rats

  Addiction Biology · 2024-05-01 · 8 citations

  articleOpen accessSenior authorCorresponding

  Neuronal ensembles in the medial prefrontal cortex mediate cocaine self-administration via projections to the nucleus accumbens. We have recently shown that neuronal ensembles in the prelimbic cortex form rapidly to mediate cocaine self-administration. However, the role of neuronal ensembles within the nucleus accumbens in initial cocaine-seeking behaviour remains unknown. Here, we sought to expand the current literature by testing the necessity of the cocaine self-administration ensemble in the nucleus accumbens core (NAcCore) 1 day after male and female rats acquire cocaine self-administration by using the Daun02 inactivation procedure. We found that disrupting the NAcCore ensembles after a no-cocaine reward-seeking test increased subsequent cocaine seeking, while disrupting NAcCore ensembles following a cocaine self-administration session decreased subsequent cocaine seeking. We then characterized neuronal cell type in the NAcCore using RNAscope in situ hybridization. In the no-cocaine session, we saw reduced dopamine D1 type neuronal activation, while in the cocaine self-administration session, we found preferential dopamine D1 type neuronal activity in the NAcCore.

  PublisherOA PDFDOI

• ERK2 Signaling in the Nucleus Accumbens Facilitates Stress Susceptibility and Cocaine Reinstatement

  Biological Psychiatry Global Open Science · 2024-11-12

  articleOpen access

  Second-messenger signaling within the mesolimbic reward circuit plays a key role in the negative effects of stress and the underlying mechanisms that promote drug abuse. Because the nucleus accumbens (NAc) integrates reward valence, we investigated how ERK2 (extracellular signal-regulated protein kinase-2) signaling affects the development of stress-related comorbidities, including negative affect and drug sensitivity. We assessed how chronic unpredictable stress influenced the phosphorylation of ERK2-signaling proteins within the NAc of male Sprague Dawley rats. Using a herpes simplex virus, we either upregulated or downregulated NAc ERK2 activation and evaluated behavioral responses to stress-eliciting stimuli (elevated plus maze, open field, forced swim test) and cocaine-seeking behavior (conditioned place preference, self-administration). We also examined ERK2-mediated modifications in spine morphology of medium spiny neurons within the NAc. Chronic unpredictable stress increased the phosphorylation of ERK2-signaling proteins within the NAc. Viral-mediated activation of NAc ERK2 enhanced susceptibility to both depression- and anxiety-related stimuli and increased cocaine-seeking behavior (conditioned place preference and reinstatement). These behavioral changes were associated with an increase in stubby and mushroom spines of NAc medium spiny neurons. Conversely, downregulation of ERK2 activation attenuated affect-related behavioral responses in the forced swim test and blunted cocaine’s rewarding effects without influencing NAc spine morphology. NAc ERK2 contributes to stress-induced behavioral deficits, including anxiety- and depression-like phenotypes, while promoting cocaine-seeking behavior. These findings suggest that ERK2 signaling in the NAc plays a role in the comorbidity of these related syndromes. This study highlights a role for ERK2 signaling in the brain’s reward center (nucleus accumbens [NAc]) in influencing behaviors related to depression and drug use. Promoting activity of this pathway within the NAc of adult rats led to more depression-like behaviors, anxiety, and increased sensitivity to cocaine. On the other hand, reducing ERK2 activity had the opposite effect, alleviating depression-like behaviors and blunting the response to cocaine. These findings suggest that this pathway plays a crucial role in the way the brain responds to both stress and drug use, highlighting potential targets for understanding and treating psychiatric comorbidities.

  PublisherDOI

• Separate gut-brain circuits for fat and sugar reinforcement combine to promote overeating

  Cell Metabolism · 2024-05-17 · 11 citations

  erratum
  PublisherDOI

• Viral-mediated expression of Erk2 in the nucleus accumbens regulates responses to rewarding and aversive stimuli

  bioRxiv (Cold Spring Harbor Laboratory) · 2023-10-03

  preprintOpen access

  Second-messenger signaling within the mesolimbic reward circuit is involved in both the long-lived effects of stress and in the underlying mechanisms that promote drug abuse liability. To determine the direct role of kinase signaling within the nucleus accumbens, specifically mitogen-activated protein kinase 1 (ERK2), in mood- and drug-related behavior, we used a herpes-simplex virus to up- or down-regulate ERK2 in adult male rats. We then exposed rats to a battery of behavioral tasks including the elevated plus-maze, open field test, forced-swim test, conditioned place preference, and finally cocaine self-administration. Herein, we show that viral overexpression or knockdown of ERK2 in the nucleus accumbens induces distinct behavioral phenotypes. Specifically, over expression of ERK2 facilitated depression- and anxiety-like behavior while also increasing sensitivity to cocaine. Conversely, down-regulation of ERK2 attenuated behavioral deficits, while blunting sensitivity to cocaine. Taken together, these data implicate ERK2 signaling, within the nucleus accumbens, in the regulation of affective behaviors and modulating sensitivity to the rewarding properties of cocaine.

  PublisherOA PDFDOI

Recent grants

• Neuronal ensembles in extinction of cocaine seeking.

  NIH · $913k · 2019–2023

Frequent coauthors

• Bruce T. Hope

  National Institute on Drug Abuse

  31 shared

• Daniele Caprioli

  Sapienza University of Rome

  31 shared

• Sergio D. Iñiguez

  30 shared

• Jennifer M. Bossert

  27 shared

• Yavin Shaham

  National Institute on Drug Abuse

  27 shared

• Marco Vènniro

  University of Maryland, Baltimore

  22 shared

• Richard Quintana‐Feliciano

  Icahn School of Medicine at Mount Sinai

  19 shared

• F. Javier Rubio

  18 shared

Education

• B.S.

  Florida State University

• M.S.

  Florida State University

• Ph.D.

  Florida State University

• Other

  National Institute on Drug Abuse