Role of hippocampal 5-HT1A receptors on elevated plus maze exploration after a single restraint experience.

A compelling finding reveals that a systemic injection of 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) can enhance exploration in an elevated plus maze after stress. In a study with rats, immediate post-stress treatment increased open arm exploration 24 hours later, while saline showed no effect. This enhancement was negated by pre-treatment with a selective 5-HT1A antagonist, suggesting that hippocampal 5-HT1A receptors play a critical role in mitigating the behavioral impacts of stress. These insights could inform future approaches to stress-related disorders.

Study at a glance

Abstract

Previous studies have shown that 2 h restraint stress induces deficits in open arm exploration of an elevated plus maze 24 h later. This effect was attenuated by a post-stress systemic injection of the 5-HT non-selective agonist, 5-methoxy-N,N-dimethyltryptamine (5-MeODMT). To verify a possible involvement of hippocampal 5-HT1A receptors in this effect, rats were stereotaxically implanted with canulae in the dorsal hippocampus. Seven days later they received bilateral microinjections of 5-MeODMT (20 nmol/0.5 microliter) or saline. No difference was found on exploration of an elevated plus maze 24 h later. However, when treatments were performed immediately after 2 h of restraint stress, the drug was able to increase open arm exploration 24 h later. This effect was antagonized by a previous microinjection of (+)WAY-100135 (40 nmol/0.5 microliter), a selective 5-HT1A antagonist. The results suggest that hippocampal 5-HT1A receptors may attenuate stress behavioral consequences.