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How Your Brain’s Reward Circuits Drive Your Choices | Dr. Robert Malenka

In this episode my guest is Robert Malenka, MD, PhD, a professor of psychiatry and behavioral sciences at Stanford School of Medicine who has made numerous seminal discoveries about how the brain changes (neuroplasticity) in response to learning and to rewarding and reinforcing experiences. We discuss the brain’s reward systems involving dopamine and serotonin and how they motivate us to seek out specific behaviors and substances. We discuss how these reward systems are modified based on context and our memories and how they can be hijacked toward maladaptive drug-seeking in addiction. We also explore how reward systems influence social connections, oxytocin and empathy and how that applies to our understanding of autism spectrum disorders. This episode should be of interest to those interested in neuroplasticity, social bonding, addiction, autism, learning and motivation. Thank you to our sponsors AG1: https://drinkag1.com/huberman ROKA: https://roka.com/huberman Levels: https://levels.link/huberman LMNT: https://drinklmnt.com/huberman Supplements from Momentous https://www.livemomentous.com/huberman Huberman Lab Social & Website Instagram: https://www.instagram.com/hubermanlab Twitter: https://twitter.com/hubermanlab Facebook: https://www.facebook.com/hubermanlab TikTok: https://www.tiktok.com/@hubermanlab LinkedIn: https://www.linkedin.com/in/andrew-huberman Website: https://hubermanlab.com Newsletter: https://hubermanlab.com/neural-network Dr. Robert Malenka Stanford academic profile: https://profiles.stanford.edu/robert-malenka Publications: https://profiles.stanford.edu/robert-malenka?tab=publications Current clinical trial: https://clinicaltrials.stanford.edu/trials/e/NCT03841682.html MapLight: https://maplightrx.com/team/robert-malenka LinkedIn: https://www.linkedin.com/in/robert-malenka-09b3a016b Articles Distinct neural mechanisms for the prosocial and rewarding properties of MDMA: https://bit.ly/3PNs2ze Oxytocin receptor is not required for social attachment in prairie voles: https://bit.ly/3XLguOZ Gating of social reward by oxytocin in the ventral tegmental area: https://bit.ly/3rigeee Anterior cingulate inputs to nucleus accumbens control the social transfer of pain and analgesia: https://bit.ly/44z3qP1 Social reward requires coordinated activity of nucleus accumbens oxytocin and serotonin: https://go.nature.com/44iOQvl Selective filtering of excitatory inputs to nucleus accumbens by dopamine and serotonin: https://bit.ly/44UG8n1 Serotonin receptor regulation as a potential mechanism for sexually dimorphic oxytocin dysregulation in a model of Autism: https://bit.ly/44DS24e 5-HT modulation of a medial septal circuit tunes social memory stability: https://go.nature.com/3rjlXk7 Other Resources MapLight: https://maplightrx.com Multidisciplinary Association for Psychedelic Studies (MAPS): https://maps.org MindMed: https://mindmed.co Timestamps 00:00:00 Dr. Robert Malenka 00:02:37 Sponsors: ROKA & Levels 00:05:21 Dopamine & Reward Circuitry 00:11:31 Reward, Arousal, Memory & Dopamine 00:17:34 Context, Cues & Dopamine Modification 00:25:38 Memory & Reward Scaling 00:30:50 Dopamine, “Addictive Liability” & Route of Administration 00:39:07 Sponsor: AG1 00:40:04 Drugs of Abuse & Brain Changes; Addiction & Individual Variability 00:50:51 Reinforcement vs. Reward, Wanting vs. Liking 00:57:50 Opioids, Psychostimulants & Dopamine 01:03:38 Sponsor: LMNT 01:04:51 Self-Doubt, Confidence & Career 01:12:40 Autism Spectrum Disorder 01:19:29 Pro-Social Interaction & Reward; Oxytocin, Serotonin & Dopamine 01:30:30 Nucleus Accumbens & Behavior Probability 01:38:28 Reward for Pro-Social Behavior 01:43:13 Social Media & “Addictive Liability”; Gambling 01:52:17 Pain, Social Behavior & Empathy 02:02:19 Empathy Circuitry, Dopamine & Serotonin 02:10:07 Autism Spectrum Disorder & Social Interactions, Empathy 02:17:23 MDMA, Serotonin & Dopamine; Addiction & Pro-Social Effects 02:28:13 Autism Spectrum Disorder, Social Behavior, MDMA & Pharmacology 02:37:18 Serotonin, MDMA & Psychedelics 02:40:16 Psychedelics: Research & Therapeutic Potential 02:47:57 Zero-Cost Support, YouTube Feedback, Spotify & Apple Reviews, Sponsors, Momentous, Social Media, Neural Network Newsletter Title Card Photo Credit: Mike Blabac - https://www.blabacphoto.com Disclaimer: https://hubermanlab.com/disclaimer

Andrew HubermanhostRobert Malenkaguest
Jul 10, 20232h 50mWatch on YouTube ↗

CHAPTERS

  1. 0:00 – 13:00

    Intro, Malenka’s Background, and Scope of the Conversation

    Huberman introduces Dr. Robert Malenka, outlining his seminal contributions to neuroplasticity, reward systems, addiction, social neuroscience, autism, and emerging work on psychedelics. They set expectations that the discussion will connect molecular mechanisms to everyday behaviors like motivation, addiction, and social connection.

  2. 13:00 – 35:00

    Dopamine 101: Reward, Salience, and Evolutionary Function

    Malenka explains what dopamine is, where key dopamine neurons live, and how the brain’s reward circuit works. He emphasizes that dopamine signals evolutionary importance and salience—not just pleasure—and is tightly linked with arousal and memory systems.

  3. 35:00 – 50:00

    Context, Prefrontal Cortex, and the Flexibility of Reward

    They discuss how context, internal state, and prior experience radically change how reward circuits respond to the same cue. Prefrontal cortex, hippocampus, amygdala, and sensory inputs converge on the nucleus accumbens to scale and reshape dopamine’s impact.

  4. 50:00 – 1:10:00

    Addiction: Drug Kinetics, Plasticity, and Individual Vulnerability

    The conversation shifts to addiction: why some drugs are more addictive than others, how kinetics of dopamine release matter, and how even single exposures can produce lasting plasticity in reward circuits. They also explore why only some users develop severe addiction.

  5. 1:10:00 – 1:22:00

    Wanting vs. Liking, Tolerance, and 12‑Step Reframing

    Malenka introduces the distinction between reinforcement (increasing behavior), reward (subjective pleasure), wanting, and liking. They connect this to clinical observations and 12‑step approaches that deliberately create reward around abstinence and sober identity.

  6. 1:22:00 – 1:42:00

    Nicotine, Personal Anecdotes, and Hidden Reinforcement Patterns

    Malenka shares a personal story about briefly smoking in Paris and still craving cigarettes in that context decades later, illustrating how powerful cue‑linked reward learning can be. They also touch on nicotine’s high addictive liability despite its social normalization.

  7. 1:42:00 – 1:59:00

    Social Reward, Evolution, and the Role of Serotonin and Oxytocin

    The focus shifts from drugs to natural social rewards. Malenka explains why his lab moved from studying addiction to social behavior, and how oxytocin and serotonin in nucleus accumbens and VTA modulate sociability. They ground social reward in evolutionary pressures.

  8. 1:59:00 – 2:25:00

    Autism Spectrum Disorder, Social Motivation, and Terminology Nuance

    They carefully discuss autism spectrum disorder (ASD), balancing respect for neurodiversity with recognition that some individuals have severe, disabling symptoms. Malenka reviews evidence that social reward processing and serotonergic systems may be altered in some forms of ASD.

  9. 2:25:00 – 2:47:00

    Empathy and Social Transfer of Pain and Relief in Mice

    Malenka describes his lab’s work on “behavioral antecedents of empathy” in mice: social transfer of pain and analgesia, and early work on generosity/compassion assays. These behaviors engage circuits also implicated in human empathy, including anterior cingulate to accumbens pathways.

  10. 2:47:00 – 3:11:00

    MDMA, Serotonin vs. Dopamine, and Social Therapies

    They dive into MDMA as a powerful probe of social and reward circuits. Malenka explains how MDMA’s stronger action on serotonin transporters—alongside dopamine—helps separate its reinforcing from its prosocial effects, and how this guides drug development for social dysfunction, including in ASD.

  11. 3:11:00

    Psychedelics, Caution, and the Future of Therapeutic Use

    In closing, Malenka shares his measured enthusiasm for psychedelic research. As a child of the 60s/70s, he sees enormous scientific and therapeutic potential but warns strongly against evangelical hype and uncontrolled use that could produce harm and backlash.

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