Lecture – What Opioids Do to the Brain, and What the Brain Will Do for Opioids

Available with English captions.

Presented by Elena H. Chartoff, PhD, McLean Hospital – The Jack H. Mendelson Memorial Research Award

This talk traces the course of Dr. Chartoff’s research into the neurobiology of substance use disorders. Her recent work looks at the ways exposure to opioids, such as heroin, morphine, and oxycodone, alter molecular and behavioral function. It also investigates how exposure to opioids can change fundamental reward and motivational processes.

To detail the many ways that opioids affect the brain, Chartoff describes several of her studies. For example, she discusses research into the stimulation of molecular pathways that increase cAMP signaling, which regulates cell functioning. This stimulation, she says, produces greater effects in opioid-withdrawn cells than it does in non-opioid-withdrawn cells.

She explains that chronic opioid exposure through inhibitory brain receptors, known as mu opioid receptors, causes changes in molecular pathways. These changes counteract the chronic inhibition of cAMP signaling. Opioid withdrawal unmasks these changes and causes an over-shoot of cAMP signaling and its downstream molecular targets.

Watch now to learn more about:

  • Intracellular molecular changes that occur in the brain due to chronic opioids
  • How withdrawal from chronic opioids produces anhedonia
  • Supposed sex differences in opioid behavioral effects

Chartoff also describes work that examines how anhedonia might contribute to maintenance of drug taking and/or relapse.

Characterized by a loss of pleasure in things that normally cause pleasure, anhedonia is a negative affective state that can be one component of depression. Chartoff points out that negative affective states contribute to negative reinforcement, and people with substance use disorder take drugs to avoid the negative affective states.

Also, Chartoff discusses her research into the effects of opioids in both males and females. Her laboratory studies involving rat subjects demonstrate that inherent sex-based differences can change addictive-like behavior.

For example, her work found that male rats initially self-administer more oxycodone than females. This suggests that male rats might find oxycodone less rewarding than females, so they need to take more of the drug to get the same rewarding effect. This is supported by the findings that females have higher levels of the enzyme that produces dopamine, and that oxycodone produces greater dopamine release in females compared to males.