Modulation of anxiety in rats evaluated in the elevated T-maze: Evidence of the relationship between substance P and diazepam

This study aimed to investigate the relationship between substance P (SP) and diazepam (DZP) in the modulation of anxiety and memory in rats as evaluated in the elevated T-maze (ETM). For this purpose, in the first experiment, rats were intraperitoneally (i.p.) pretreated with saline or DZP (1 mg/kg) and 25 min later they were intracerebroventricularly (i.c.v.) injected with PBS or SP (10 pmol). In the second experiment, rats were i.p. pretreated with saline or DZP (1 mg/kg) and 25 min later were i.c.v. injected with FK888 (100 pmol, a NK1 antagonist). After 1 min, animals were i.c.v. injected with vehicle (PBS + ethanol 10%) or SP (10 pmol). Our results show that DZP significantly decreased the latency to leave the enclosed arm of the ETM in the test and re-test session, indicating an anxiolytic and an amnesic effect, respectively. Although the central administration of SP did not significantly alter ‘per se’ the latency to leave the enclosed arm of the ETM in the test and re-test sessions, there was a trend to increase this parameter in the test session (indicating an anxiogenic-like effect). Furthermore, SP was able to reverse, via NK1 receptors, the effect produced by DZP during the test session. Moreover, none of the treatments interfered in the one-way escape behavior recorded in the test or re-test session in the ETM. In conclusion, our results strengthen and extend previous experimental data showing an interaction between the tachykinergic and benzodiazepine–GABA systems in the modulation of anxiety.