Evaluation of the anxiolytic-like effect of NKP608, a NK1-receptor antagonist, in two rat strains that differ in anxiety-related behaviors

Rationale: NKP608, a selective NK1 receptor antagonist, has been shown to produce anxiolytic-like effects in rodents tested in different anxiety models. However, most of these findings are based on social behaviors and, to our knowledge, there is no report concerning the effects of NKP608 in the elevated plus-maze (EPM) and the open field (OF), two classical models of anxiety/emotionality. Moreover, this compound has never been tested in rodent strains that display contrasting levels of anxiety-related behaviors.

Objectives: To investigate the anxiolytic-like effects of NKP608 in Lewis and SHR inbred rats, proposed as a genetic model of anxiety for showing high and low indices of anxiety, respectively.

Methods: Lewis and SHR rats of both sexes were tested in the EPM and OF tests following acute administration of NKP608 (0.003, 0.03 or 0.3 mg/kg) or chlordiazepoxide (CDZ, 5 mg/kg). Measures of approach/avoidance towards the open arms of the EPM and the central area of the OF were used as indices of anxiety.

Results: All doses of NKP608 produced anxiolytic-like effects, similar to those of CDZ, in SHR males tested in the OF but not in the EPM. Conversely, this compound had a partial anxiolytic effect in LEW males (and, to a lower degree, in SHR females) in the EPM, but not in the OF. LEW females were unaffected following all pharmacological treatments.

Conclusions: These findings indicate that the anxiety-related effects of NKP608 are strain-, sex- and test-dependent. Moreover, the present data confirm and extend the therapeutic potential of NK1 receptor antagonists for the treatment of anxiety.