25579
Social and Non-Social Reward in Mouse Models of Autism
The social motivation theory of autism posits that social interaction may be less rewarding for individuals with ASD than typically-developing individuals. However, it has also been suggested that reward processing may be affected more globally in ASD. Mouse models present a promising opportunity to explore how these competing explanations may apply in a variety of ASD etiologies, including ASD-associated genetic mutations. The Fmr1 knockout mouse model of Fragile X Syndrome has been previously shown to exhibit deficits in reward learning, and here we extend these findings to several other genetic models including Celf6 and Nf1 mutants, representing an ASD candidate gene and syndromic form of ASD respectively.
Objectives:
We employed the conditioned place preference assay to measure reward learning in several genetic mouse models of ASD, with the goal of establishing whether any deficits are global or specific to social rewards.
Methods:
In the conditioned place preference assay, mice are conditioned to associate one side of a three-chamber apparatus with a particular reward. Time spent on this side of the apparatus is compared before and after conditioning, and a significant increase indicates that the animal was sufficiently rewarded to learn the association. To assess non-social reward, we injected the mice with cocaine on the conditioned side and saline on the opposite side. Acute locomotor sensitization to cocaine was also measured by total distance traveled in the drug-paired side on each day of conditioning. A social reward version of this task is ongoing, in which mice are exposed to social interaction instead of cocaine.
Results:
Consistent with the global reward impairment hypothesis, cocaine conditioning was not observed in the Celf6 knockout line, indicating a general lack of reward response. Celf6 knockout mice did not show a significant preference for the cocaine-associated chamber after three days of conditioning, in contrast to wildtype littermates. They also did not exhibit typical cocaine sensitization during conditioning, suggesting a lack of acute response to the reward. We also examined reward conditioning and acute responses in the Nf1+/- model of neurofibromatosis, a syndromic form of ASD.
Conclusions:
We have confirmed global reward learning abnormalities among a subset of genetic mouse models, suggesting that reward deficits in ASD may exist beyond impaired social motivation.