Our results suggest that aptamer treatment was selective in mitigating the behavioral effects of peripheral MK-801 administration. These findings can best be put into the context of a model concerning neural mechanisms underlying schizophrenia as developed by Carlsson and colleagues reduces GABA inhibitory control of midbrain dopaminergic neurons causing elevated dopamine output at terminal projection sites. The work of Holahan et al., showed that MK-801 administration was associated with reduced neural activation in the infralimbic cortex and elevated extinction pressing that was blocked by dopamine receptor antagonists. Therefore, MK-801 may increase rates of midbrain dopamine neural activity by reducing cortical glutamaterigic control leading to enhanced dopamine-dependent behaviors such as perseveration. An alternative interpretation for the behavioral effect of MK801 is that it altered a more fundamental motivational state enhancing the conditioned reinforcing properties of the conditioned cues. Indeed, MK-801 has been shown to prolong progressive ratio responding compared to saline-injected controls and MK-801 potentiates both food unconditioned and conditioned behavioral responses. This could occur for a number of reasons including elevations in dopamine efflux in the Acb, a deficit in signaling processes that participate in termination of eating-satiety signals, or, as hypothesized in the present report, induction of a non-specific preservative effect on ongoing behavior. In any case, the behavioral changes observed can be ascribed to elevations in dopamine output in the Acb; the target of the aptamer injections. In the current report, rats Gefitinib inquirer treated with 0.1 mg/ kg MK-801 systemically and either tris-buffer vehicle or the random oligonucleotide sequence into the nucleus accumbens showed higher rates of lever pressing during extinction than rats treated systemically with saline. The MK-801- injected group pre-treated with a 200 nM dose of the aptamer into the nucleus accumbens pressed significantly less than the MK-801 groups that received vehicle or the random oligonucleotide sequence pre-treatment in the nucleus accumbens. Furthermore, there were no significant difference in extinction pressing between groups that received central 0 nM or 200 nM aptamer pre-treatment and saline, rather than MK-801, peripheral administration. This, in conjunction with the finding that the 200 nM dose of aptamer did not affect incorrect lever pressing or locomotor activity, suggests that aptamer pretreatment was selective in reversing, or at least minimizing, the cognitive-behavioral deficits of peripheral MK-801 administration. The cross maze used to test locomotion was not one with open and closed arms as would be used to test anxiety but rather, one with all closed arms minimizing anxiety-eliciting effects.