Temozolomide treatment inhibits spontaneous motivation for exploring a complex object in mice: A potential role of adult hippocampal neurogenesis in “curiosity”

Abstract

Intrinsic exploratory biases are an innate motivation for exploring certain types of stimuli or environments over others, and they may be associated with cognitive, emotional, and even personality‐like traits. However, their neurobiological basis has been scarcely investigated. Considering the involvement of the hippocampus in novelty recognition and in spatial and pattern separation tasks, this work researched the role of adult hippocampal neurogenesis (AHN) in intrinsic exploratory bias for a perceptually complex object in mice. Spontaneous object preference tasks revealed that both male and female C57BL/6J mice showed a consistent unconditioned preference for exploring “complex”—irregular—objects over simpler ones. Furthermore, increasing objects’ complexity resulted in an augmented time of object exploration. In a different experiment, male mice received either vehicle or the DNA alkylating agent temozolomide (TMZ) for 4 weeks, a pharmacological treatment that reduced AHN as evidenced by immunohistochemistry. After assessment in a behavioral test battery, the TMZ‐treated mice did not show any alterations in general exploratory and anxiety‐like responses. However, when tested in the spontaneous object preference task, the TMZ‐treated mice did not display enhanced exploration of the complex object, as evidenced both by a reduced exploration time—specifically for the complex object—and a lack of preference for the complex object over the simple one. This study supports a novel role of AHN in intrinsic exploratory bias for perceptual complexity. Moreover, the spontaneous complex object preference task as a rodent model of “curiosity” is discussed.

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“…Observational scoring was carried out by a trained observer who was blind to the mice's sex or experimental condition and had no previous assumptions about the study's outcome. Behavioral assessment was carried out following previously reported protocols [43][44][45][46]. On the first day of behavioral assessment (i.e., Day 22 of the experiment), we evaluated motility and anxiety-like behavior in the elevated plus maze (EPM).…”