The chick separation stress paradigm: a validation study.

To expand the generalizability of the chick separation stress paradigm as a high-throughput anxiolytic screen, six positive drug probes (doses in mg/kg: meprobamate 15-120, pentobarbital 2.5-20.0, chlordiazepoxide 2.5-15.0, buspirone 2.5-10.0, imipramine 1-15, and clonidine 0.10-0.25) and five negative drug probes (amphetamine 0.5-4.0, scopolamine 0.2-1.6, caffeine 5-20, chlorpromazine 1-30, and haloperidol 0.03-1.00) were evaluated in the test. Seven-day-old chicks received intramuscular injections of either vehicle or drug probe 15 min prior to tests in either a mirror (low-stress) or a no-mirror (high-stress) condition for a 3-min observation period. The dependent measures were distress vocalizations to index separation stress and sleep onset latency to index sedation. All positive drug probes attenuated distress vocalizations in a dose-dependent manner, except buspirone. All positive drug probes affected sleep onset latency in a dose-dependent manner, except buspirone and imipramine. In all cases, the anxiolytic-like effect of positive drug probes was greater than its sedative effect. None of the negative drug probes affected either distress vocalizations or sleep onset latency, except for the highest dose of amphetamine, which caused pronounced stereotypy. These findings demonstrate that this anxiolytic screen is sensitive to a wide range of positive pharmacological probes and insensitive to a wide range of negative pharmacological probes.