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Stress-Induced Pathophysiology 251This type of conditioned association is dependent on the state of the dopaminesystem. In order to test this, we found that two odors may be sequentially conditionedwith footshock. This enables us to test the ability of a neuron to exhibitconditioning to a footshock, then perform a manipulation of the dopamine system,and examine whether the manipulation affects the pairing that has alreadyoccurred, or if it interferes with new conditioning. Using this paradigm, administrationof a control solution such as a saline injection between conditioning sessionsdid not interfere with either the amplitude of the previous conditionedresponse when the odor is presented alone, or with the ability to condition a responseto a new odor paired with a footshock. If a dopamine antagonist is administeredsystemically prior to the second odor, we found that there was also nointerference with the previously conditioned response. However, there was a completeblockade in the ability to condition the second odor to the footshock. Therefore,dopamine appears to be required for conditioning to occur; on the other hand,once the conditioning is present, dopamine is no longer required to maintain theconditioned response.The prefrontal cortex also is capable of modulating the conditioning. If theprefrontal cortex is stimulated electrically following the first conditioning procedure,there is no interference with the conditioned response when the odor is thenpresented alone. However, if the prefrontal cortex is stimulated during the pairingof the second odor with the footshock, there is an inability to obtain a conditionedresponse to the odor. Therefore, the prefrontal cortex appears to affect thesystem in the opposite manner as does dopamine, in that dopamine is required fornew conditioning to occur, but the prefrontal cortex is capable of suppressing newconditioning. On the other hand, once a conditioned response is present, neitherprefrontal cortical activation nor dopamine receptor blockade has an effect (Rosenkranz& Grace, 2002b).Drawing from the previous results, one might expect a deficit in prefrontalcortical function to cause the system to show an abnormally high level of associationsof a pathological nature. Indeed, schizophrenia patients are known to makeinappropriate associations. On the other hand, it has been suggested that one ofthe effects of antipsychotic drugs is to prevent schizophrenia patients from makingnew inappropriate associations; however, the associations already present arenot affected (Kapur, 2003). This could be a behavioral reflection in the humanschizophrenia patient of the conditioned processes observed in the amygdala ofthe anesthetized rat.Chronic Stress and Amygdala ActivityThe research just reviewed further confirms the involvement of the amygdala inaversive events and its plasticity in response to these learned events (LeDoux,