Thus blocking its association with chromatin and its repressive effect on target gene expression. Given the fact that Fep1 and multidomain CGFS monothiol glutaredoxins can form homodimers, a dimer of Fep1 may associate with two Grx4 molecules. Under conditions of iron excess, two GRX domains of Grx4 could themselves coordinate a cluster, making the N-terminal region of Fep1 available for interaction with chromatin. Interestingly, a number of studies have shown that Grx4 plays a role in conveying the information of the presence of iron to Php4. In fact, disruption of grx4+ leads to constitutive activation of Php4, making iron-regulated genes that are under its control to be continually repressed, irrespective of cellular iron status. Under high iron conditions, the GRX domain of Grx4 interacts with Php4 in an iron-dependent manner. This association between GRX domain and Php4 fosters the inactivation and release of Php4 from the Php2/Php3/Php5 complex and its subsequent export from the nucleus to the cytoplasm by exportin Crm1. In contrast, under iron deficiency, the GRX domain dissociates from Php4, allowing Php4 to bind to the Php2/Php3/ Php5 heterotrimeric complex, which represses transcription of iron-using genes. In S. cerevisiae, Aft1 is a major iron-responsive transcription factor that activates the expression of genes involved in iron metabolism, including the high-affinity iron uptake genes. Aft1 trans-activates gene expression under iron starvation conditions but its activity is inhibited under iron-replete conditions. A number of studies have shown that the multidomain CGFS monothiol glutaredoxins Grx3 and Grx4 are required for irondependent inhibition of Aft1. Drugs can influence motivated behavior in multiple ways. For example, as argued by Caggiula and others, the reinforcing properties of nicotine are due to a combination of three actions: the ability of the drug to act as a primary reinforcer, the ability of the drug to establish CSs as conditioned reinforcers through Pavlovian associations, and the ability of the drug to act as a reinforcement enhancer, thereby magnifying the incentive value of accompanying stimuli, even if they are conditioned or unconditioned reinforcers. Similar findings have been reported with other drugs, which suggest that one behavioral mechanism of CS control over drug-taking behavior is the enhancement of the conditioned reinforcing properties of a CS by the drug. Here we show that amphetamine enhances reinforcing efficacy regardless of the cues’ initial incentive value. This broad effect on behavior may be unique to psychostimulants compared to other drugs, and may be related to its ability to enhance the reinforcing efficacy of a broad class of cues. For example, the ability of nicotine to enhance the reinforcing effect of visual stimuli was systematically related to the strength of the reinforcer. Our results suggest this is not the case for amphetamine.