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INNOSC Theranostics and
Pharmacological Sciences Youth brain health check and dysregulation

(BHCo). The advent of molecular neurobiological tools to with elevated expression during adulthood. Perinatal THC
uncover neurotransmitter cascade surfeits or deficits and exposure also resulted in shorter latency to the first active
possibilities for restoring dopamine balance across these lever press, greater responses to low heroin doses, and more
brain regions, including the PFC, can improve screening heroin-seeking during mild stress and after extinction.
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of cognitive abilities, which would enhance prevention and Studies by Yuan et al., and others reveal that persistent
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intervention approaches. However, implementing changes alterations in neuronal signaling and cognitive ability
in educational programs requires top-down public policy result from chronic nicotine exposure, likely due to altered
strategies. A detailed description of our proposed BHC can dopamine function in the brain. Dopamine D receptor
2
be found in Braverman et al. 86 activation of fast-spiking interneurons in the PFC does not
occur until late adolescence, along with the recruitment
8. Epigenetics of reward processing in and maturation of local GABAergic activity. 99,100 In
adolescence addition, Tseng and O’Donnell point out that D -NMDA
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1
It is widely acknowledged that the adolescent brain receptor interactions in cortical pyramidal neurons
matures through a prolonged reorganization of gray that are necessary for mature cognitive and attentional
processing continue to develop during this period. Flores-
matter, white matter, and associated neurochemical Barrera et al. discovered that ventral hippocampal input
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systems. Interestingly, this period of enhanced cognitive to the medial PFC is strengthened during late adolescence
ability in adolescents coincides with a reduction in due to the D receptor-mediated emergence of NMDA
cortical gray matter thickness, resulting from epigenetic 1
experience-dependent loss of synapses and a concomitant receptor GluN2B subunit function. Unfortunately, in
strengthening of the remaining connections. 87-89 In the mesolimbic system, particularly in the NAc, D and
1
addition, during adolescence, gray matter volume and D receptor responses are immature, leading to reduced
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synaptic interaction between NAc and the PFC.
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density decrease in the brain, specifically in the parietal Furthermore, the stimulation of the D receptor has an
cortex, PFC, and basal ganglia, all of which are critical age-specific influence on AMPA-evoked cell excitability,
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for executive function, motivated behaviors, and sensory and interactions between D and AMPA receptors elicit the
processing. 34,90,91 Furthermore, Paus demonstrated activation of GABA interneurons, primarily in adults but
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2
that there were corresponding increases in white not adolescents. In summary, these observations suggest
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matter, potentially reflecting augmented myelination a functional switch in reward processing during adolescent
and axonal diameter, leading to enhanced efficiency of development mediated by dopamine regulation of GABA
impulse transduction. Notably, Gogtay et al. observed interneurons. It is well known that enhanced GABA
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that phylogenetically older brain regions mature earlier transmission following chronic alcohol intake significantly
than the newer ones. This delayed, uneven maturation reduces dopamine release at the NAc. In addition,
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of subcortical, emotional, and reward-focused systems, stimulation of GABAB receptors inhibits dopaminergic
including cortical executive and impulse control systems, VTA neurons. However, Pandey’s group demonstrated
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could underlie many RDS behaviors, including SUD. 93-95
that the inhibition of VTA neuronal firing by bath‐applied
The prevalence of mental health disorders, including GABA is primarily mediated by GABAA receptors. 106
addictive behaviors, in children and adolescents has The risk of all addictive drug and non-drug behaviors,
increased at least two- to three-fold from the 1990s especially in the unmyelinated PFC of adolescents, is both
to the present day. According to Monaco, one critical and complex. Many animal and human studies have
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plausible mechanistic reason for this increase may be highlighted the epigenetic impact on the developing brain
the transmission of altered brain circuits epigenetically in adolescents compared to adults. Some studies reveal an
across generations through non-DNA-based mechanisms underlying hyperdopaminergia, which predisposes young
(intergenerational and transgenerational effects). These individuals to risky behaviors by inducing high quanta
epigenetic insults to the developing brain may be due presynaptic dopamine release at reward site neurons. In
to a family history of SUD, obesity, or a poor diet (e.g., addition, altered reward gene expression in adolescents
processed, palatable foods). These insults may cause caused by epigenetically transferred social defeat, such as
intergenerational and transgenerational effects for at least bullying, can persist into adulthood. However, there is also
up to 2 years, influencing set points in neuropathways evidence that overstimulating epigenetic events can elicit
integrating sensory-motor, reward, and feeding behaviors.
adolescent hypodopaminergia. This complexity (Figure 2)
In line with this, Hurd’s group linked parental THC suggests that neuroscience cannot definitively claim that all
exposure in rats to reduced proenkephalin mRNA adolescents carry a hyperdopaminergic trait. To help dissect
expression in the NAc during early development, along these seemingly opposing views, Blum’s laboratory reported

Volume 7 Issue 2 (2024) 8 doi: 10.36922/itps.1472