A University of Pennsylvania grad researcher has found that teenagers who smoke tobacco are at higher risk for addiction to morphine, heroin, or fentanyl, because early nicotine exposure increases the “reward” feeling from opioid drugs:
The link between early-life nicotine use and OUD is not well understood, so for her PhD in the labs of John Dani and Amelia Eisch, former NGG student Ruthie Wittenberg wanted to understand how nicotine use during adolescence could change the brain to promote morphine reward in adulthood.
Adolescence is the time in development when the brain is more flexible and with greater plasticity than in adulthood. One such part of the brain, the ventral tegmental area (VTA), is considered to be the start of the main reward pathway. Increased neuronal activity, altered dopamine signaling, and structural changes are examples that all contribute to increased reward sensitivity. Evidence from both human and animal studies indicate that using drugs during adolescence, when the brain is most flexible, can create long-lasting changes in the brain and in behavior that can extend into adulthood.
To understand how adolescent nicotine exposure changes reward-related behaviors in adulthood, Ruthie gave adolescent mice nicotine for 2 weeks and waited until they were older to see how they responded to opioids, like morphine. She wanted to see how adult mice who had been exposed to nicotine earlier in life responded to the rewarding properties of opioids compared to mice who had never been exposed to nicotine.
…
To understand the link between using nicotine in adolescence and morphine later in adulthood, Ruthie looked at the VTA, the origin of the reward pathway. The VTA is made up of neurons that release one or more neurotransmitters to communicate with each other. It is also well-known for producing dopamine, which motivates the seeking of drugs and other rewards. Additionally, the VTA releases other neurotransmitters, like GABA, which helps to quiet other neurons, like those that release dopamine. Since the brain is really flexible in adolescence, Ruthie wanted to know if changes in VTA GABA neurons could be a link between nicotine use in adolescence and morphine use in adulthood.
Chronically using nicotine in adolescence changes how VTA GABA neurons communicate with other neurons. Ruthie wanted to know how adolescent nicotine use changes how VTA GABA neurons respond to morphine in adulthood. As a result, she used patch-clamp electrophysiology to record the electrical activity of these neurons. An important thing to note is that opioids like morphine bind to endogenous opioid receptors, meaning receptors mice already have on their VTA GABA neurons. When morphine acts on these receptors, it inhibits neural activity. Moreover, GABA neurons quiet the VTA dopamine neurons and morphine quiets GABA neurons, allowing dopamine neurons to release more dopamine, leading to the rewarding effects of morphine. This process is called disinhibition, where the neurons that inhibit (GABA neurons) are inhibited themselves, which allows other neurons to start to fire.
…
By recording from GABA and dopamine neurons in the VTA in adult mice, she found that among mice exposed to nicotine as adolescents, morphine no longer inhibited GABA neurons and it also did not change how dopamine neurons fired.