Social animals detect the affective states of conspecifics and utilize this information to orchestrate social interactions. In a novel social affective preference text in which experimental adult male rats could interact with either naive or stressed conspecifics, the experimental rats either approached or avoided the stressed conspecific, depending upon the age of the conspecific. Specifically, experimental rats approached stressed juveniles but avoided stressed adults. Inhibition of insular cortex, which is implicated in social cognition, and blockade of insular oxytocin receptors disrupted the social affective behaviors. Oxytocin application increased intrinsic excitability and synaptic efficacy in acute insular cortex slices, and insular oxytocin administration recapitulated the behaviors observed toward stressed conspecifics. Network analysis of Fos immunoreactivity in 29 regions identified functional connectivity between insular cortex, prefrontal cortex, amygdala and the social decision-making network. These results implicate insular cortex as a key component in the circuit underlying age-dependent social responses to stressed conspecifics.

BACKGROUND: Studies using continuous access drug self-administration showed that cocaine seeking increases during abstinence (incubation of cocaine craving). Recently, studies using intermittent access self-administration showed increased motivation to self-administer and seek cocaine. We examined whether intermittent cocaine self-administration would potentiate incubation of craving in male and female rats, and the estrous cycle's role in this incubation. METHODS: In Experiment 1, male and female rats self-administered cocaine either continuously (8-h/d) or intermittently (5-min ON, 25-min OFF × 16) for 12 days, followed by relapse tests after 2 or 29 days. In Experiments 2-3, female rats self-administered cocaine intermittently for 6, 12, or 18 sessions. In Experiment 4, female rats self-administered cocaine continuously followed by relapse tests after 2 or 29 days. In Experiments 3-4, the estrous cycle was measured using a vaginal smear test.

Social animals detect the affective states of others and utilize this information to orchestrate appropriate social interactions. Social affective behaviors include cooperation, reproductive acts and avoiding sick individuals. In a social affective behavioral test in which experimental adult male rats were given the choice to interact with either naive or stressed conspecifics, the experimental rats demonstrated both approach and avoidant behaviors towards the conspecific, depending upon the age of the conspecific; experimental adult rats approached the stressed juvenile but avoided the stressed adult. Optogenetic inhibition of the insular cortex, a region anatomically positioned to contribute to social cognition, disrupted these behaviors. Receptors for the social nonapeptide oxytocin (OT) are found in high density within the insular cortex and here oxytocin increased intrinsic excitability and synaptic efficacy in acute insular cortex slices. Blockade of oxytocin receptors (OTRs) in the insula eliminated the effect of conspecific stress on approach behavior, while insular administration of OT recapitulated the behaviors typically observed in response to stressed conspecifics. Network analysis using Fos immunoreactivity identified functional connectivity between the insular cortex and the network of regions involved in social decision making. These results implicate insular cortex as a novel target of OT and suggest that insula is a key component in the circuit underlying age-dependent social responses to stressed conspecifics.Social animals, including humans, have an enormous repertoire of behavioral expressions that provide for the transmission of one's affective state to other members of the group 1-3 . Sensory and perceptive systems in the "social decision-making network" (SDMN) which consists of the social brain network 4 and the mesolimbic reward system 5 allow one to appraise these social stimuli and integrate them with past experiences, situational, and somatic factors to shape specific behavioral responses 6 . In addition to the SDMN, growing evidence implicates insular cortex in responding to socioemotional stimuli in humans. When tasked to identify the emotion of another from a facial expression, or to observe another suffer a painful stimulation, a reliable neural correlate is relative increase in the blood oxygen level dependent (BOLD) signal in the insular cortex 7,8 . Accordingly, emotion recognition and empathic deficits have been reported among individuals with insular cortex lesions [9][10][11][12] . Empathic processes are also disrupted in autism spectrum 1 Department of Psychology, Boston College, Chestnut Hill, MA 02467, USA 2 These authors made equal contributions to this work. *Corresponding Author: John P. Christianson, Department of Psychology, Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA 02467 USA, Email: j.christianson@bc.edu, Phone: +1-617-552-3970.A note about the preprint. This manuscript was submitted to bioRxiv.org after multiple rounds of peer review. The manuscrip...

The prefrontal cortex is involved in goal-directed behavior. Here, we investigate circuits of the PFC regulating motivation, reinforcement, and its relationship to dopamine neuron activity. Stimulation of medial PFC (mPFC) neurons in mice activated many downstream regions, as shown by fMRI. Axonal terminal stimulation of mPFC neurons in downstream regions, including the anteromedial thalamic nucleus (AM), reinforced behavior and activated midbrain dopaminergic neurons. The stimulation of AM neurons projecting to the mPFC also reinforced behavior and activated dopamine neurons, and mPFC and AM showed a positive-feedback loop organization. We also found using fMRI in human participants watching reinforcing video clips that there is reciprocal excitatory functional connectivity, as well as co-activation of the two regions. Our results suggest that this cortico-thalamic loop regulates motivation, reinforcement, and dopaminergic neuron activity.