Light Dark

Like the EPM, the light-dark test is an ethological model that relies on both the innate aversion of rodents to brightly illuminated areas and their tendency to exhibit spontaneous locomotor behavior in response to novel environments.39 The typical apparatus has two connected compartments, one is lit (aversive area) and the other is darkened (safe area), with an opening between the two compartments. This test was developed using male mice and the C57BL/6J and SW-NIH strains are the best strains in which to evaluate the potential anxiolytic effect of new chemical entities (NCEs). Mice are placed in the light area and then begin moving along the periphery of the compartment until they locate the opening to the dark compartment. The time the animal spends moving, rearing, and transitioning from the dark to light area is recorded over a 5-10 min period. Anxiolytics increase locomotion and time spent in the light area while anxiogenic compounds have opposite effects. While BZs are reliably detected in this model as being anxiolytic, the sedative effects of this class of compounds at high doses can confound the results. Inverse agonists at the GABAA site also produce anxiogenic effects in the light-dark test. There is controversy concerning the effectiveness of drugs that modulate 5HT neurotransmission in this test. Drugs acting on 5HT1 receptors (e.g., buspirone) work in this test, but tend to do better in conflict-based models (see below). 5HT2 agonists and 5HT3 antagonists show anxiolytic effects in this model, while SSRIs tend to be ineffective.40

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