Understanding the adolescent brain
Experiments in male rats shed light on how parts of the brain involved in addiction differ during adolescence.
During adolescence, chemicals and cells in the brain undergo significant reorganization. These changes are thought to be why teenagers are often more vulnerable to developing drug addictions and psychiatric disorders. However, it is not fully understood how the brain transforms during this transitional period.
Most of this reorganization takes place in the dopamine system which is responsible for triggering pleasurable sensations, including the feeling of reward after taking drugs. In 2020, a group of researchers found that adolescent male rats released less of the chemical dopamine in a part of the brain involved in the reward pathway than adult rats. But it was unclear what was causing this age-related effect.
To investigate, Iacino et al. — including some of the researchers involved in the 2020 study — blocked a family of receptors called nAChRs (short for nicotinic acetylcholine receptors) in the brain cells of male rats. These receptors bind to a neurotransmitter, called acetylcholine, which stimulates cells to release dopamine. Iacino et al. found that inhibiting a specific type of nAChR led to a decrease in dopamine in adult rats, but an increase in early adolescent rats. However, this effect was not observed when other types of nAChRs were inhibited.
Iacino et al. found that the adolescent male rats also had higher levels of another neurotransmitter, called GABA, which blocks the release of dopamine. This led them to hypothesize that the reduced levels of dopamine in early adolescence may be due to increased levels of GABA, which is secreted by specialized cells which also have nAChRs on their surface.
To investigate, Iacino et al. blocked two receptors for GABA that are found on dopamine-releasing neurons before exposing the rats to the nAChR inhibitor. This caused the adolescent rats to release less dopamine following nAChR inhibition, similar to the levels observed in adult rats. These findings suggest that the nAChR inhibitor leads to a rise in dopamine by stopping cells from releasing GABA — but only in adolescent rats.
The work of Iacino et al. demonstrates how the dopamine system differs in adolescence, which may provide new insights into why teenagers are often more susceptible to addiction. For instance, nicotine, the addictive substance in cigarettes, can also bind to nAChRs and make them less sensitive to acetylcholine. This may reduce the release of GABA, resulting in more dopamine being released, which is then sensed as a reward by the teenage brain. However, more research is needed to fully understand how this brain circuit is modulated by nicotine intake.
Originally published at https://elifesciences.org/digests/62999.