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

KEYPOINTS

• 01

  The reward circuit evolved to tag what matters for survival

  Malenka, a Stanford psychiatrist and neuroscientist, describes dopamine neurons in the ventral tegmental area (VTA) projecting to the nucleus accumbens. This system marks food, water, sex and social contact as worth pursuing again. Drugs of abuse 'trick' it into treating an experience as vital for survival, which is why they can generate such compulsive repetition.

• 02

  Route of administration drives addictive liability

  You can't become addicted to something you never take, and how you take it matters. Smoking or injecting cocaine or methamphetamine gets the drug into the brain almost instantly and produces a rapid, powerful dopamine surge in the accumbens lasting seconds to minutes. Malenka links this to the crack epidemic and today's meth crisis. He notes our brains didn't evolve to handle drugs that potent, or synthetic opioids like fentanyl.

• 03

  Drugs remodel reward synapses using normal learning machinery

  Work from Malenka's lab and others shows cocaine, methamphetamine, morphine and heroin cause powerful plasticity at synapses onto dopamine neurons and accumbens neurons. The changes resemble those used in adaptive learning and memory. The circuit is highly plastic and can become sensitized to particular experiences.

• 04

  Who becomes addicted is a mix of genes and environment

  Many people use a substance without developing a problem. Malenka attributes the difference to genetics, current environment and the environment you grew up in, all of which shape the reward circuitry. Availability of a substance in a society also strongly shapes which addictions become widespread.

• 05

  Reinforcing is not the same as rewarding; wanting is not liking

  Something is reinforcing if it makes you repeat the behavior, and rewarding if it actually feels good. Kent Berridge and Terry Robinson's 'wanting versus liking' distinction explains a friend's description of cocaine: 'I hate it, but I want to do it again.' The same pattern shows up in destructive relationships. Huberman suggests 12-step programs may work partly by building a liking for sobriety that outcompetes the wanting.

• 06

  Cues tied to powerful experiences can trigger cravings for decades

  Because reward circuitry is closely linked to memory, places and contexts become reinforcing in their own right. Malenka tells of smoking for a few weeks in Paris at around 20, then not smoking after returning home. Forty years later, he still craves a cigarette every time he goes back to Paris.

• 07

  Oxytocin and serotonin make social interaction reinforcing

  Building on decades of prairie vole work by Larry Young and Tom Insel showing that oxytocin in the accumbens supports pair bonding, Malenka's lab found oxytocin there promotes sociability in mice by triggering serotonin release. Oxytocin also modulates dopamine neurons in the VTA. Malenka acknowledges a recent paper questioned oxytocin's role in pair bonding, and urges weighing it against 30 years of contrary evidence and its own methodological limits.

• 08

  MDMA's pro-social and addictive effects may use different systems

  MDMA reverses the serotonin and dopamine transporters, the 'vacuum cleaners' that normally clear these molecules, so they pump the molecules out. It favors serotonin roughly 70/30 or 80/20. Malenka's hypothesis, supported so far in mouse empathy models, is that its addictive liability runs mostly through dopamine while its pro-social and empathogenic effects run through serotonin, notably the 5-HT1B receptor in the accumbens.

• 09

  Gambling is uniquely tied to hope

  Casinos employ people to tune slot-machine payout schedules for maximum return visits. Huberman relays a gambling addict's insight: unlike an alcoholic or cocaine user, a gambler believes the next bet could change everything for the better.