Dopaminergic Modulation of Forced Running Performance in Adolescent Rats: Role of Striatal D1 and Extra-striatal D2 Dopamine Receptors

Abstract

Improving exercise capacity during adolescence impacts positively on cognitive and motor functions. However, the neural mechanisms contributing to enhance physical performance during this sensitive period remain poorly understood. Such knowledge could help to optimize exercise programs and promote a healthy physical and cognitive development in youth athletes. The central dopamine system is of great interest because of its role in regulating motor behavior through the activation of D1 and D2 receptors. Thus, the aim of the present study is to determine whether D1 or D2 receptor signaling contributes to modulate the exercise capacity during adolescence and if this modulation takes place through the striatum. To test this, we used a rodent model of forced running wheel that we implemented recently to assess the exercise capacity. Briefly, rats were exposed to an 8-day period of habituation in the running wheel before assessing their locomotor performance in response to an incremental exercise test, in which the speed was gradually increased until exhaustion. We found that systemic administration of D1-like (SCH23390) and/or D2-like (raclopride) receptor antagonists prior to the incremental test reduced the duration of forced running in a dose-dependent manner. Similarly, locomotor activity in the open field was decreased by the dopamine antagonists. Interestingly, this was not the case following intrastriatal infusion of an effective dose of SCH23390, which decreased motor performance during the incremental test without disrupting the behavioral response in the open field. Surprisingly, intrastriatal delivery of raclopride failed to impact the duration of forced running. Altogether, these results indicate that the level of locomotor response to incremental loads of forced running in adolescent rats is dopamine dependent and mechanistically linked to the activation of striatal D1 and extra-striatal D2 receptors.

Prosomeric Hypothalamic Distribution of Tyrosine Hydroxylase Positive Cells in Adolescent Rats

“…In addition, this period is characterized by a larger gain in weight and adipose tissue content compared to the young adult stage (Kutsenko et al, 2021). Accurate characterization of the distribution of TH-positive cells in the hypothalamic region during the adolescent period is important for experimental designs aiming to determine their action during modulation of motor and metabolic responses in this period of life (Caballero and Tseng, 2016;Toval et al, 2017Toval et al, , 2020Toval et al, , 2021Kutsenko et al, 2021). The aim of the present study was to map more precisely the distribution of THpositive neurons in specific nuclei or strata of the hypothalamic region in adolescent rats following the updated area map provided by the prosomeric model (Puelles et al, 2012a;Ferran et al, 2015a;.…”

Regulation of Voluntary Physical Activity Behavior: A Review of Evidence Involving Dopaminergic Pathways in the Brain

“…Although forced running differs from voluntary running in terms of brain adaptations and psychological state [29], systemic administration of D1-like and D2-like receptor antagonists either separately or in combination decreases forced running wheel behavior. However, when administered directly into the striatum of rodents, only the D1-like receptor antagonist decreases the duration of forced running wheel performance [30]. These findings implicate a role of extra-striatal D2 receptors and intra-striatal D1 receptors [30].…”

Adenosine A2A and dopamine D2 receptor interaction controls fatigue resistance

“…The traditional view of striatal dopaminergic signaling suggests a primary role for D 1 R, but the simplistic dichotomy of behaviors influenced by D 1 R and D 2 R in medium spiny neurons is being reevaluated (Soares-Cunha et al, 2016). The improvement of performance with increased Frontiers in Pharmacology frontiersin.org forced running is linked to dopamine and specifically to the activation of striatal D 1 R and extrastriatal D 2 R (Toval et al, 2021). Additionally, the dorsolateral prefrontal cortex has been proposed as important during exhaustive exercise (Bigliassi and Filho, 2022).…”