The role of dopamine and endocannabinoid systems in prefrontal cortex development: Adolescence as a critical period

Abstract

The prefrontal cortex plays a central role in the control of complex cognitive processes including action control and decision making. It also shows a specific pattern of delayed maturation related to unique behavioral changes during adolescence and allows the development of adult cognitive processes. The adolescent brain is extremely plastic and critically vulnerable to external insults. Related to this vulnerability, adolescence is also associated with the emergence of numerous neuropsychiatric disorders involving alterations of prefrontal functions. Within prefrontal microcircuits, the dopamine and the endocannabinoid systems have widespread effects on adolescent-specific ontogenetic processes. In this review, we highlight recent advances in our understanding of the maturation of the dopamine system and the endocannabinoid system in the prefrontal cortex during adolescence. We discuss how they interact with GABA and glutamate neurons to modulate prefrontal circuits and how they can be altered by different environmental events leading to long-term neurobiological and behavioral changes at adulthood. Finally, we aim to identify several future research directions to help highlight gaps in our current knowledge on the maturation of these microcircuits.

The Effects of Peripubertal THC Exposure in Neurodevelopmental Rat Models of Psychopathology

“…MAM or pTHC exposure also induced alterations in the transcriptional regulation of the genes encoding for cannabinoid CB1 ( Cnr1 ), dopamine D2 ( Drd2 ) or D3 ( Drd3 ) receptors at the level of PFC of adult rats, further confirming the hypothesis of DA–cannabinoid interaction as a molecular substrate of neurodevelopmental disorders [ 24 ]. However, MAM or pTHC exposure differentially affected the DNA methylation at Cnr1 or Drd2 gene regulatory regions, which were not always followed by significant alterations in gene expression.…”

Developmental trajectory of social reward motivation from early adolescence into adulthood in female and male Long‐Evans rats

“…The general consensus in the literature is that adolescents are more sensitive to rewarding stimuli and less sensitive to aversive stimuli than are adults (Doremus-Fitzwater & Spear, 2016;Peters & Naneix, 2022).…”

“…The opposite pattern was found for another endocannabinoid's (2‐arachidonoylglycerol) concentrations in the prefrontal cortex (Ellgren et al., 2008). The density of endocannabinoid receptors CB1 and CB2 peak around the time of onset of puberty in female (∼P33) and male rats (∼P40) (reviewed in Peters & Naneix, 2022; Schneider, 2008). The oxytocinergic system also modulates social behavior, including social reward (Menon & Newman, 2023), and its receptor densities increase significantly in early adolescence and into adulthood (Hammock, 2015).…”

Balance of Activity during a Critical Period Tunes a Developing Network

“…How neurons measure levels of activity during the CP remains under active investigation (Zeng et al ., 2021; Carreira-Rosario et al ., 2021; Giachello et al ., 2021; Coulson et al ., 2022; Reh et al ., 2020; Peters and Naneix, 2022; Gibel-Russo, Benacom and Di Nardo, 2022). The second messenger calcium is likely to be involved, as calcium signalling is central to activity-regulated plasticity during nervous system development, including adjustment to changing internal and external environments, as well as learning and memory (Spitzer, 2012).…”