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;.…”

A Handful of Details to Ensure the Experimental Reproducibility on the FORCED Running Wheel in Rodents: A Systematic Review

“…However, that lack of response can be solved by applying a habituation phase prior to an exercise program (18). This period improves the capacity of rodents to maintain a higher volume and intensity of running and establishes a homogeneous starting point for all the animals to perform a training program (18,161). In addition, the habituation protocol reduces non-specific stress responses in rats that can modify the physiological and behavioral results in forced models (19).…”