Absence of social conditioned place preference in BTBR T+tf/J mice: relevance for social motivation testing in rodent models of autism.

A major goal of translation research in autism is to characterize the physiological and psychological processes underlying behavioral abnormalities. Since autism reflects impairments in social motivation, we modified the mouse three-chamber social approach apparatus for use as a social conditioned place preference arena. We paired one of two unique contexts with social interactions in juvenile mice for five or ten conditioning sessions in BTBR T+tf/J mice and a control strain with normal approach behaviors (C57BL/6J) since the BTBR T+tf/J inbred mouse strain displays a variety of behavioral alterations analogous to symptoms of autism spectrum disorders. While C57BL/6J mice formed a conditioned place preference to the context associated with social interactions, particularly those receiving ten days of conditioning, BTBR T+tf/J mice did not. Neither absence of social proximity nor avoidance due to high rates of autogrooming appeared to underlie the impaired positive incentive value of the unconditioned social stimulus in the BTBR T+tf/J strain. These data contribute to a growing body of evidence suggesting that the BTBR T+tf/J strain shows impairments in all diagnostic domains of autism including social motivation. Additionally, social conditioning testing might provide an important social motivation measure in other rodent models of neuropsychiatric disorders characterized by social abnormalities.

The importance of the basolateral/basomedial amygdala for goal-directed maternal responses in postpartum rats.

A model of the neural regulation of maternal behavior in rats proposes that the basolateral amygdala (BLA) provides pup-related sensory inputs to the nucleus accumbens-ventral pallidum (NA-VP) circuit and that medial preoptic area activation of the mesolimbic dopamine system potentiates the ability of BLA neurons to stimulate goal-directed maternal responses, such as pup retrieval behavior. Previous research using electrical lesions has provided some direct support for the importance of BLA. In the current study, we examined the effects of temporary inactivation of neurons within BLA and the adjoining basomedial nucleus of the amygdala (BMA) on maternal behavior in postpartum rats. For an anatomical control, muscimol was injected into the medial amygdala (MeA). Since research has shown that MeA plays an inhibitory role in maternal behavior, it was predicted that muscimol injections restricted to that site would not disrupt maternal behavior. The results showed that muscimol injections into BLA/BMA, at dosage levels between 100 and 200 ng/side, produced major deficits in retrieval behavior and minor deficits in nursing behavior. In contrast, muscimol injections into MeA left maternal behavior relatively unaffected. These results show that neuron-specific inactivation of BLA/BMA causes severe deficits in what can be considered a goal-directed and appetitive maternal response, pup retrieval, while leaving the consummatory aspect of maternal behavior, nursing, relatively unaffected. Since oxytocin is important for maternal behavior, and since both BMA and MeA neurons contain OT-binding sites, perhaps OT stimulates BMA output and suppresses MeA output to influence aspects of maternal behavior.