Several lines of evidence suggest that the balance of large-scale excitatory and inhibitory neurotransmission is vastly different in adolescents compared to adults. Levels of GABA, the main inhibitory neurotransmitter in the brain, increases linearly through adolescence in rat forebrain (Hedner et al., 1984). The expression of the activating glutamate NMDA receptors on fast-spiking neurons (thought to be inhibitory interneurons) changes dramatically in the PFC of adolescents. At this time the vast majority of fast-spiking interneurons exhibit no synaptic NMDA receptor-mediated currents (Wang and Gao, 2009). Additionally the modulatory impact of dopamine-receptor binding shifts during adolescence (O'Donnell and Tseng, 2010). It is only by this time that the activation of dopamine D2 receptors increases interneuron activity (Tseng and O'Donnell, 2007). Furthermore, the synergistic interaction between dopamine D1 receptor activation and the NMDA receptor changes during adolescence, allowing for plateau depolarizations which may facilitate context-dependent synaptic plasticity (O'Donnell and Tseng, 2010; Wang and O'Donnell, 2001). These adolescent dopamine, glutamate, and GABA signaling changes suggest fundamental neural activity differences in the adolescent brain. All of these systems are essential to cognitive and emotional processes. Their dysfunction is implicated in numerous psychiatric illnesses ranging from mood disorders and addiction to schizophrenia.
