5-HT1A receptors of the lateral septum regulate inhibitory avoidance but not escape behavior in rats.

Serotonin in the lateral septum (LS) has been implicated in the modulation of defensive behaviors and in anxiety. However, it is currently unknown whether changes in 5-HT mechanisms in this brain area may selectively affect defensive responses associated with specific subtypes of anxiety disorders recognized in clinical settings. To address this question, we evaluated the effect of the intra-LS injection of the 5-HT(1A/7) receptor agonist 8-OH-DPAT (0.6, 3.0, 15.0 nmol) in male Wistar rats exposed to the elevated T-maze animal model of anxiety. This test allows the measurement of two behavioral defensive responses in the same rat: inhibitory avoidance and escape behavior. In clinical terms, these responses have been respectively related to generalized anxiety and panic disorder. The effects of 8-OH-DPAT were compared to those caused by a standard anxiolytic compound, the benzodiazepine receptor agonist midazolam (MDZ, 20 nmol). We also investigated whether the intra-LS injection of the 5-HT(1A) receptor antagonist WAY-100635 (0.37 nmol) was able to block the effects of 8-OH-DPAT. All animals were also tested in an open field for locomotor activity assessments. Results showed that whereas intra-LS administration of MDZ decreased avoidance latencies, suggesting an anxiolytic action, 8-OH-DPAT caused the opposite effect. Neither drug affected the escape performance. Intra-LS administration of WAY-100635 blocked the anxiogenic effect caused by 8-OH-DPAT. No changes to locomotion were detected in the open field. The data suggests that LS 5-HT(1A) receptors are involved in the control of inhibitory avoidance behavior and that a failure in this regulatory mechanism may be of importance to the physiopathology of generalized anxiety disorder.

Effects of chronic treatment with a water-alcohol extract from Erythrina mulungu on anxiety-related responses in rats.

We investigated the effects of chronic oral treatment with a water-alcohol extract from the inflorescence of Erythrina mulungu (Leguminosae-Papilionaceae) (EM, 50, 100, 200 mg/kg) in rats submitted to different anxiety models: the elevated T-maze (ETM, for inhibitory avoidance and escape measurements), the light/dark transition, and the cat odor test. These models were selected for their capacity to elicit specific subtypes of anxiety disorders as recognized in clinical practice. Treatment with EM impaired inhibitory avoidance latencies in a way similar to the reference drug, diazepam (DZP). Additionally, both EM and DZP increased the number of transitions and the time spent in the lighted compartment of the light/dark transition model. Furthermore, neither EM nor DZP altered behavioral responses of rats to a cloth impregnated with cat odor. In contrast to DZP, however, EM also altered ETM one-way escape. These results were not due to motor alterations since no significant effects were detected in the number of crossings or rearings in the arena. The present observations suggest that chronic EM exerts anxiolytic-like effects in defensive behaviors related to generalized anxiety and panic disorder. Although alkaloids appear to be one of the main constituents of EM, the possible mechanisms through which the extract exerts its anxiolytic action should be further investigated.