Neuroanatomical substrates mediating the aversive effects of D-1 dopamine receptor antagonists

An unbiased place preference conditioning procedure was used to examine the secondary reinforcing effects of selective D-1 dopamine (DA) receptor antagonists and the neuroanatomical substrates mediating these effects. Systemic administration of SCH-23390 or the non-benzazepine D-1 receptor antagonist A-69024 produced dose-related conditioned aversions for the drug-associated place. In contrast, the D-2 antagonists spiperone and (-)sulpiride were without effect. SCH-23390-induced place aversions were also observed after intracerebroventricular administration. The minimum dose producing this effect was significantly lower than that after systemic injection. Aversive effects were also observed after microinjection of SCH-23390 into the n. accumbens. In contrast, microinjections of this antagonist into the ventral tegmental area, caudate putamen or medial prefrontal cortex were without effect. These data confirm that the blockade of D-1 but not D-2 DA receptors induces aversive states. Furthermore, they suggest that D-1 receptors in the n. accumbens may play an important role in the regulation of non-drug induced affective states.