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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 9, 20232h 50mWatch on YouTube ↗

At a glance

WHAT IT’S REALLY ABOUT

Dopamine, Serotonin, And Social Bonds: How Reward Shapes Behavior

  1. Andrew Huberman interviews psychiatrist and neuroscientist Dr. Robert Malenka about how the brain’s reward and social circuits work, with a focus on dopamine, serotonin, and oxytocin.
  2. They explain how the dopamine system evolved to tag experiences as important, driving learning, motivation, addiction, and social behavior, and how context and plasticity radically reshape its function over time.
  3. Malenka describes addiction as drug‑driven hijacking of normal reward learning, discusses individual vulnerability, and shows how drugs like MDMA expose distinct roles for dopamine versus serotonin in reinforcement and social connection.
  4. The conversation extends to social reward, empathy, autism spectrum disorder, and emerging psychedelic therapies, emphasizing both scientific promise and serious cautions around over‑hyping or unsafe use.

IDEAS WORTH REMEMBERING

5 ideas

Dopamine marks importance and salience, not just pleasure

Dopamine neurons in the ventral tegmental area (VTA) project to the nucleus accumbens and other regions to signal that something in the environment is important—not merely pleasurable. They fire during highly rewarding events (food, sex, drugs) but also during aversive or painful events. This signal boosts arousal and memory encoding, increasing the probability that we repeat—or avoid—certain behaviors in the future.

Addictive liability depends on both amount and speed of dopamine

The risk that a drug becomes addictive (“addictive liability”) scales with how much dopamine it releases in the nucleus accumbens and how rapidly that release occurs. Route of administration is critical: smoking or injecting cocaine or methamphetamine causes an almost instantaneous, massive dopamine surge compared to snorting or oral use, dramatically increasing compulsive use risk. Single drug exposures can induce plastic changes in reward circuits lasting days to weeks, and repeated use amplifies and prolongs these changes.

Wanting and liking can diverge, explaining compulsive but unenjoyable use

Drugs and rewarding behaviors can become powerfully reinforcing even when they stop feeling good. Malenka highlights the behavioral distinction: ‘reinforcing’ means a stimulus increases the probability of repeating the behavior; ‘rewarding’ means it actually feels good. With addiction, cravings (wanting) often persist or intensify even as subjective pleasure (liking) declines—people can “hate it and still want to do it again.”

Reward circuits are highly plastic and context‑dependent

The same cue can flip from appetitive to aversive depending on recent history—Huberman’s Thanksgiving example: turkey and pie smells are enticing before the meal and repulsive afterward. This flexibility arises because dopamine and accumbens neurons receive inputs from hippocampus (memory), amygdala (emotion), prefrontal cortex (rules, planning), and sensory areas. Prior experiences with a cue (e.g., donuts, drugs, people) reshape how reward circuits respond to that cue in the future.

Social interaction is a major natural activator of reward circuitry

Non‑aggressive, non‑sexual social interactions are strongly reinforcing in social species and engage the same reward circuitry as food and drugs. Malenka’s lab and others show that oxytocin and serotonin act within the nucleus accumbens and VTA to enhance social reward, and that dopamine is released during positive social contact. Evolutionarily, social reward supports mating, cooperative child‑rearing, protection from predators, and emotional buffering.

WORDS WORTH SAVING

5 quotes

It’s not an accident that sugary, high‑fat foods are highly reinforcing. There has to be a mechanism in the brain that tells us that.

Dr. Robert Malenka

A single administration of a drug of abuse like cocaine or morphine can cause changes in reward‑circuit connections that last days to weeks.

Dr. Robert Malenka

You can’t develop a problem with a substance if you never take it. By definition.

Dr. Robert Malenka

Liking something means it actually feels good. Wanting means you work to get it again. And those can come apart.

Dr. Robert Malenka

What is more important for the survival of the human species than empathy and compassion?

Dr. Robert Malenka

Dopamine and the brain’s reward circuitry (VTA–nucleus accumbens–prefrontal networks)Addiction, drug kinetics, and neuroplastic changes in reward systemsContext, memory, and prefrontal modulation of wanting vs. likingSocial reward, oxytocin, serotonin, and the neurobiology of sociabilityEmpathy and “social transfer” of pain and relief in animal modelsAutism spectrum disorder, social motivation, and serotonergic therapeuticsPsychedelics and MDMA as probes of brain function and potential treatments

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