Comparing dopamine release, uptake, and D2 autoreceptor function across the ventromedial to dorsolateral striatum in adolescent and adult male and female rats

Abstract

Adolescents have increased vulnerability for the development of a range of psychiatric disorders, including substance abuse disorders (SUD) and mood disorders. Adolescents also have increased rates of sensation seeking and risk taking. The mesolimbic dopamine system plays a role in all these behaviors and disorders and reorganization of the dopamine system during adolescence may be important in mediating these developmental changes in behavior and vulnerability. Here, we used ex vivo fast scan cyclic voltammetry to examine developmental differences in dopamine release and its local circuitry regulation across the striatum. We found that adolescents have significantly decreased dopamine release in the nucleus accumbens core across a range of stimulation frequencies that model tonic and phasic firing of mesolimbic dopamine neurons. We show this is not mediated by differences in rate of dopamine uptake, but may be driven by hypersensitive dopamine autoreceptors, indicated by increased inhibition in dopamine release following agonism of D2/D3 receptors, in the adolescent nucleus accumbens core. Additionally, we observed increases in dopamine uptake in the dorsomedial striatum. No other significant differences between release, uptake, or D2 autoreceptor function was observed between adolescent and adult rats in all brain areas tested (nucleus accumbens shell, nucleus accumbens core, dorsomedial striatum, and dorsolateral striatum). These developmental differences in dopamine release may be important in mediating some of the unique behavioral repertoire seen in adolescents, such as increases in sensation seeking, and its associated vulnerabilities..

A unique multi-synaptic mechanism regulates dopamine release in the nucleus accumbens during adolescence

“…In the present report, we utilized ex vivo FSCV to compare stimulated dopamine release and its regulation in the NAc core of adult and adolescent male rats. Replicating our previous findings (Pitts et al, 2020), we see decreased stimulated dopamine release in the NAc core of male early adolescent rats. We also found this decrease in stimulated dopamine release is not driven by differences in release probability or transporter function (i.e.…”

“…While reports examining extracellular levels of dopamine in the striatum show both lower and higher levels of dopamine during adolescence (Badanich et al, 2006;Cao et al, 2007;Philpot et al, 2009), sub-second stimulated dopamine release is consistently found to be decreased in the striatum of adolescent rats (Stamford, 1989;Palm and Nylander, 2014;Pitts et al, 2020). We have previously shown that stimulated dopamine release is decreased in the nucleus accumbens (NAc) core of early adolescent male rats (Pitts et al, 2020), yet, what mechanism is differentially mediating dopamine release in adolescent and adult rats is still unclear.…”

“…Since previous research from our lab showed that the NAc core has the largest difference in stimulated dopamine release between adult and adolescent male rats (Pitts et al, 2020), we focused this report on understanding the mechanisms mediating dopamine release in that region. This is of particular importance because the NAc core is important in regulating reward-related learning and goal-directed decision making (Di Chiara, 2002;Saddoris et al, 2013), which are altered in adolescence.…”

Adolescent dopamine neurons represent reward differently during action and state guided learning

“…Motivated actions are mediated by dopamine release from the terminals. Mechanisms that govern dopamine release and volume transmission may be different in adults and adolescents (Robinson et al, 2011; Pitts et al, 2020). Our observation of increased dopamine neuron phasic response to reward in Pavlovian conditioning but decreased, phasic response in operant conditioning could be functionally amplified or muted if dopamine release is different in response to similar phasic activation of these neurons.…”

The Dopaminergic Control of Movement-Evolutionary Considerations

“…Much like in mammals, lamprey’s SNc/VTA dopaminergic neurons express D 2 receptors [ 3 ]. Dopamine release in the SNc/VTA is controlled by D 2 autoreceptors [ 53 ], and this mechanism is therefore very likely present in lampreys as well. The lamprey SNc/VTA population consists of around 600 dopaminergic neurons [ 41 ], a seemingly low number, but which is in line with the percentage of SNc/VTA neurons found in mammals, not taking the large cortical expansion into account in the latter [ 41 , 54 ].…”