Serotonergic innervation of the hippocampus and nucleus accumbens septi and the anxiolytic-like action of the 5-ht 3 receptor antagonists

Abstract

The roles of hippocampus (HP) and the nucleus accumbens septi (NAS) in the anxiolytic activity of two 5-HT 3 receptor antagonists were studied in two animal models of anxiety, in rats. Injection of tropisetron (0.005 and 0.01 μg) or ondansetron (1.0 and 2.5 μg) into the hippocampus increased punished consumption of water in the Vogel conflict test. In the open field test neither 5-HT 3 receptor antagonists had anxiolytic-like effects. Tropisetron (0.01 and 0.025 μg) injected into the NAS caused a marked increase in punished drinking, while ondansetron (0.01–15.0 μg) had no effect. In the open field test, tropisetron (0.001, 0.005 and 0.01 μg) and ondansetron (1.0 and 2.5 μg) given to the NAS increased the number of entries into the central part of the open-field, and the time spent in the central sector of the arena. Depletion of 5-HT significantly enhanced the anxiolytic-like effect of intra-NAS-injected tropisetron in the open field, at the dose of 0.005 μg. Moreover, 5,7-DHT lesions produced a tendency to increase motor activity in tropisetron-treated rats. Both hippocampal and accumbens 5-HT 3 receptors seem to contribute to the anxiolytic-like effects of 5-HT 3 antagonists in the Vogel test. It also appears that this effect of 5-HT 3 receptor antagonists is related to their action on postsynaptic 5-HT 3 receptors within the NAS, and depends on the functional state of the 5-HT innervation ascending from the raphe nuclei. Thus, the present data add more arguments for the more specific involvement of this limbic nucleus in emotional control.