The 5-HT2A, 5-HT5A, and 5-HT6 serotonergic receptors in the medial prefrontal cortex behave differently in extinction learning: Does social support play a role?

Studies on the social modulation of fear have revealed that in social species, individuals in a distressed state show better recovery from aversive experiences when accompanied - referred to as social buffering. However, the underlying mechanisms remain unknown, hindering the understanding of such an approach. Our previous data showed that the presence of a conspecific during the extinction task inhibited the retrieval of fear memory without affecting the extinction memory in the retention test. Here, we investigate the role of serotonergic receptors (5-HTRs), specifically 5-HT2A, 5-HT5A, and 5-HT6 in the medial prefrontal cortex (mPFC), In the retention of extinction after the extinction task, in the absence or presence of social support. Extinction training was conducted on 60-day-old male Wistar rats either alone or with a conspecific (a familiar cagemate, non-fearful). The antagonists for these receptors were administered directly into the mPFC immediately after the extinction training. The results indicate that blocking 5-HT5A (SB-699551–10 μg/side) and 5-HT6 (SB-271046A - 10 μg/side) receptors in the mPFC impairs the consolidation of CFC in the social support group. Interestingly, blocking 5-HT2A receptors (R65777 - 4 μg/side) in the mPFC led to impaired CFC specifically in the group undergoing extinction training alone. These findings contribute to a better understanding of brain mechanisms and neuromodulation associated with social support during an extinction protocol. They are consistent with previously published research, suggesting that the extinction of contextual fear conditioning with social support involves distinct neuromodulatory processes compared to when extinction training is conducted alone. •During the extinction task, social buffering inhibits fear retrieval without impairing the retention of extinction memory.•The extinction of CFC with social support depends on 5-HT5A and 5-HT6 serotonergic receptors in the mPFC.•Ritanserin (a 5-HT2A receptor antagonist) infused in the mPFC impairs extinction retention in the alone group.