Neuronal activity and the expression of hypothalamic oxytocin and vasopressin in social versus cocaine conditioning

• ICR mice produced CPP when conditioned with unfamiliar conspecific or cocaine alone.
• Subject mice reduced preference for conspecific in conspecific versus cocaine conditioning.
• The expression of c-Fos-IR neurons in conspecific or cocaine conditioning alone differed from that in conspecific versus cocaine conditioning.
• The subject mice undergoing different conditioning showed differential expression of OT and AVP in the PVN and SON.

Although drug rewards and natural rewards share neural substrates, the neuronal activation patterns and mechanisms behind the interaction between cocaine and social reward are poorly understood. Here, we investigated the conditioned place preference (CPP) in social (conspecific) vs cocaine conditioning, and the expression of central c-Fos, hypothalamic oxytocin (OT) and vasopressin (AVP) in ICR mice. We found that the mice produced CPP when conditioned with unfamiliar conspecific or cocaine alone. However, the mice failed to produce CPP when the two stimuli were concurrently conditioned. Compared to conditioning with conspecific alone, the mice decreased preference for conspecific when conditioning with social vs cocaine. We observed differential expression of c-Fos-immunoreactive neurons in the ventral anterior cingulate cortex, posterior cingulate cortex, accumbens (shell and core), medial nucleus of the amygdale and the ventral pallidum when comparing the control (CK), social (SC) or cocaine conditioning (CC) group, and social vs cocaine conditioning (SCC) group. Compared to the CK group, the SC or CC group had higher OT expression in the paraventricular nucleus (PVN) and lower AVP expression in the PVN and supraoptic nucleus. The SCC group showed lower OT expression compared to the SC group, and higher OT and AVP expression in the PVN compared to the CC group. These results indicate that cocaine impairs social preference through competing with social reward. The differential activations of neurons within specific reward areas, and differential expression of OT and AVP are likely to play an important role in mediating the interaction between social and cocaine rewards.