Dynorphinergic lateral hypothalamus to posterior ventral tegmental area pathway matures after adolescence in male...

The highly plastic nature of the adolescent brain is well-known, and is thought to contribute to the unique susceptibility of adolescents to drugs of abuse. However, much investigation of adolescent plasticity has been focused on synaptic plasticity, as synapses are strengthened and pruned. Here, we show that dynorphin⁺ neurons in the lateral hypothalamus of adolescent male rats do not respond to low doses of intravenous combined nicotine + ethanol, while male adult lateral hypothalamus dynorphin⁺ neurons do. We also provide evidence that the dynorphinergic projection from the lateral hypothalamus to the posterior ventral tegmental area is not present in adolescent males, suggesting that axons are still extending during this time. Together, these results suggest a mechanism for the increased susceptibility of adolescent male rats to drug reward.