Conflict Models

There are two types of conflict tests, both of which involve conditioned and punished responses. In the Geller-Seifter (GS) test, food-deprived rats are trained to press a lever for food and when the animals reach a stable state of lever pressing for the food, a shock component is introduced such that responding for food also elicits a mild electric shock (conflict component). NCEs with anxiolytic activity release the suppression of the punished response.41 An important parameter of the test is that it measures punished as well as nonpunished responding so that an assessment of the potential motor effects of the NCE can be evaluated within the test session itself. This test has proven invaluable for evaluating the potential anxiolytic properties of NCEs, but requires a lengthy daily training period before an NCE can be evaluated. An alternative conflict model is the Vogel conflict test (VCT), in which water-deprived rats receive a mild shock from the spout of the test bottle during portions of the test session. This model circumvents the long training process required for the GS test but because it does not measure nonpunished as well as punished responses, there should be a thorough examination of whether the NCE under evaluation has motor or analgesic properties since these effects could confound the test results. Both models have good predictive validity with GABAa, serotonergic, glutamatergic, and adrenergic compounds producing reversal of the punished response in both paradigms.42

The four-plate test is an animal model of anxiety in which novel exploratory behavior in novel surroundings is suppressed by delivering mild foot shock to plates that are organized into four quadrants.43 Similar to the VCT and GS tests described above, administration of standard anxiolytic drugs such as diazepam and alprazolam, as well as the SSRIs (e.g., sertraline, citalopram) and serotonin-norepinephrine reuptake inhibitors (SNRIs; e.g., milnacipran, venlafaxine) produce a significant increase in punished responding.44

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