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. 2025 May;242(5):955-964.
doi: 10.1007/s00213-023-06419-2. Epub 2023 Jul 10.

Noradrenergic modulation of play in Sprague-Dawley and F344 rats

Stephen M Siviy  1 , Michelle A Martin  2 , Celeste M Campbell  2
Affiliations

Noradrenergic modulation of play in Sprague-Dawley and F344 rats

Stephen M Siviy et al. Psychopharmacology (Berl). 2025 May.

Abstract

Rationale: For many mammals, engaging in social play behavior as a juvenile is important for cognitive, social, and emotional health as an adult. A playful phenotype reflects a dynamic interplay between genetic framework and experiences that operate on hard-wired brain systems so the relative lack of play in an otherwise playful species may be useful for identifying neural substrates that modulate play behavior. The inbred F344 rat has been identified as a strain that is consistently less playful than other strains commonly used in behavioral research. Norepinephrine (NE) acting on alpha-2 receptors has an inhibitory effect on play and F344 rats differ from a number of other strains in NE functioning. As such, the F344 rat may be particularly useful for gaining insight into NE involvement in play.

Objective: The objective of this study was to determine whether the F344 rat is differentially sensitive to compounds that affect NE functioning and that are known to affect play behavior.

Methods: Using pouncing and pinning to quantify play, the effects of the NE reuptake inhibitor atomoxetine, the NE alpha-2 receptor agonist guanfacine, and the NE alpha-2 receptor antagonist RX821002 on play behavior were assessed in juvenile Sprague-Dawley (SD) and F344 rats.

Results: Atomoxetine and guanfacine reduced play in both SD and F344 rats. RX821002 increased pinning to a comparable extent in both strains but F344 rats were more sensitive to the play-enhancing effects of RX821002 on pounces.

Conclusions: Strain differences in NE alpha-2 receptor dynamics may contribute to the lower levels of play in F344 rats.

Keywords: Alpha-2 adrenoceptor; F344; Genetics; Inbred; Norepinephrine; Play.

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Conflict of interest statement

Declarations. Conflicts of interest: On behalf of all authors, the corresponding author states that there is no conflict of interest.

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