Induction of reversible bidirectional social approach bias by olfactory conditioning in male mice

ABSTRACT

Social avoidance is a common component of neuropsychiatric disorders that confers substantial functional impairment. An unbiased approach to identify brain regions and neuronal circuits that regulate social avoidance might enable development of novel therapeutics. However, most paradigms that alter social avoidance are irreversible and accompanied by multiple behavioral confounds. Here we report a straightforward behavioral paradigm in male mice enabling the reversible induction of social avoidance or approach with temporal control. C57BL/6J mice repeatedly participated in both negative and positive social experiences. Negative social experience was induced by brief social defeat by an aggressive male CD-1 mouse, while positive social experience was induced by exposure to a female mouse, each conducted daily for five days. Each social experience valence was conducted in a specific odorant context (i.e. negative experience in odorant A, positive experience in odorant B). Odorants were equally preferred pre-conditioning. However, after conditioning, mice sniffed positive experience-paired odorants more than negative experience-paired odorants. Furthermore, positive- or negative-conditioned odorant contexts increased or decreased, respectively, the approach behavior of conditioned mice toward conspecifics. Because individual mice undergo both positive and negative conditioning, this paradigm may be useful to examine neural representations of social approach or avoidance within the same subject.

KEYWORDS:

• Social interaction
• associative learning
• social avoidance
• social approach
• olfactory conditioning
• olfaction

Acknowledgments

The authors would like to dedicate this work in memory of Jeremy Richman. We thank Yann Mineur for helpful discussion regarding the experiments and analysis, and Nadia Spasov and Samantha Sheppard for excellent technical support.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by grants from the National Institute of Mental Health [K23MH116339 (A.S.L.), R01MH077681 (M.R.P.)]; National Institute on Drug Abuse [R01DA014241 (M.R.P.)]; the Kavli Summer Undergraduate Research Fellowship (J.C.); the Davenport College Richter Summer Fellowship (J.C.); and the Tufts University Summer Research Fellowship (D.S.).