Social disruption-induced stress pre-exposure aggravates, while the presence of conspecifics diminishes, acetic acid-induced writhing.

Abstract

This study was undertaken to assess the modulating effects of (1) pre-exposure to repeated social disruption and (2) group testing on writhing associated with visceral pain induced by intraperitoneal administration of acetic acid. Six consecutive days of social disruption were used to prime for stress, while group testing referred to 3 mouse cage-mates receiving the acetic acid-induced writhing test as a group. Social disruption-induced stress-pre-exposed mice displayed a greater number acid-induced writhes compared to mice not receiving the pre-exposure. However, mice displayed fewer acid-induced writhes in a triad group vs. individually, suggesting group-mediated writhing-reducing effects. Likewise, group testing prevented the stress pre-exposure escalation in acid-induced writhes. Additional studies revealed that the stress-pre-exposed mice had increased expression in accumbal TRPV1 receptors. Systemic (0.25mg/kg) and bilateral intra-accumbal (0.2ng/0.2µl/side) administration of SB366791, a TRPV1 receptor antagonist, reliably prevented the stress pre-exposure escalation in acid-induced writhing; SB366791 treatment alone did not affect acid-induced writhing, stress pre-exposure anxiety-like behavior, or the group testing effects. Furthermore, lower neuronal activation was found in the medial septal nucleus in group vs. individual tested mice. Intra-medial septum (0.2µg/0.5µl) infusion with bicuculline, a GABAA receptor antagonist, effectively prevented group-mediated writhing-reducing effects, but not individual acid-induced writhing effects. These findings suggest that social disruption-induced stress pre-exposure may upregulate accumbal TRPV1 receptor expression and consequently aggravate acid-induced writhing. Group testing prevents such stress pre-exposure escalation of acid-induced writhing most likely by strengthening the GABAergic inhibition on local neural activity in the medial septum.