5-HT2A receptor activation in the dorsolateral septum facilitates inhibitory avoidance in the elevated T-maze

Serotonin in the lateral septum has been implicated in the modulation of defense and hence in anxiety. However, it deserves investigation how changes in 5-HT-mechanisms in this area modulate defensive responses associated with specific subtypes of anxiety disorders. We evaluated the effects of intra-dorsolateral septum (DLS) injections of the preferential 5-HT2A receptor agonist DOI (8 and 16 nmol), the 5-HT2C selective agonist MK-212 (0.1 and 1 nmol) and the preferential 5-HT2A antagonist ketanserin (10 and 20 nmol) in rats exposed to the elevated T-maze (ETM), a model which allows the measurement of two defensive responses: inhibitory avoidance and escape. These responses have been respectively related to generalized anxiety and panic disorder. All animals were tested in an open-field after the ETM for locomotor activity assessments. Results showed that intra-DLS DOI increased avoidance latencies, an anxiogenic effect. MK and ketanserin were without effect. Also, none of the drugs administered affected the escape performance. Ketanserin blocked the anxiogenic effect caused by DOI. No changes to locomotion were observed. The data suggests that DLS 5-HT2A receptors are involved in the control of inhibitory avoidance and that a failure in this mechanism may be of importance to the physiopathology of generalized anxiety.

► The 5-TH2A agonist DOI intra-dorsolateral septum facilitates avoidance.
► This effect is blocked by the preferential 5-TH2A antagonist ketanserin.
► Escapes responses, related to panic disorder, are not modified.
► The selective 5-HT2C agonist MK-212 does not alter avoidance or escape responses.
► 5-HT2A receptors of the dorsolateral septum play a selective role in anxiety.