Limited anxiolytic-like effects of non-benzodiazepine hypnotics in rodents

The present experiments compared the anxiolytic-like effects of the benzodi azepine (BZD) hypnotic triazolam with those of four non-BZD hypnotics inclu ding one non-selective (zopiclone) and three omega(1)-BZD selective (zolpid em, zaleplon and SX-3228) receptor ligands, in classical animal models incl uding conflict tests (punished lever pressing and punished drinking tests i n rats) and exploratory models (elevated plus-maze test in rats and light/d ark choice test in mice), and a recently developed mouse defence test batte ry (MDTB) which has been validated for the screening of anxiolytic drugs. R esults from both conflict procedures showed that zopiclone (0.3-10 mg/kg) p roduced anxiolytic-like effects comparable to those of triazolam (0.1-3 mg/ kg), whereas the selective omega(1)-BZD receptor hypnotics zolpidem (0.3-3 mg/kg), zaleplon (0.1-3 mg/kg) and SX-3228 (0.1-1 mg/kg) displayed weaker a nd/or non-specific anxiolytic-like effects. Similarly, in the light/dark te st in mice, zolpidem (0.1-1 mg/kg), zaleplon (0.3-10 mg/kg) and SX-3228 (0. 03-0.3 mg/kg) showed a reduced potential to produce anxiolytic-like effects as compared to the non-selective omega-BZD receptor hypnotics triazolam (0 .03-1 mg/kg) and zopiclone (1-30 mg/kg). In the elevated plus-maze test, zo piclone (1-10 mg/kg), zolpidem (0.1-1 mg/kg), zaleplon (0.3-3 mg/kg) and SX -3228 (0.1-1 mg/kg) displayed anxiolytic-like activity at doses close to th ose producing behavioural impairment, whereas triazolam (0.03-1 mg/kg) exhi bited anxiolytic-like effects over a wide dose range in the absence of decr eases in general activity. In the MDTB, zaleplon (0.3-10 mg/kg) decreased a ll defensive responses, a profile which was similar to that of triazolam (0 .03-1 mg/kg), while zopiclone (1-30 mg/kg), zolpidem (0.3-10 mg/kg) and SX- 3228 (0.03-1 mg/kg) had fewer effects on defensive behaviours with several effects occurring only at motor-impairing doses. Taken together, these resu lts demonstrate that, although selective omega(1)-BZD receptor hypnotics di splay anxiolytic-like activity, the effects are generally weaker than those observed with non-selective omega-BZD receptor selective hypnotics such as triazolam or zopiclone. In particular, the anxiety-reducing potential of t he omega(1)-BZD receptor selective compounds is limited to certain anxiety measures and may be confounded and/or masked by behavioural suppression.