Individual locomotor response to novelty predicts selective alterations in D1 and D2 receptors and mRNAs

Rats that have a greater locomotor response to novelty (high responders, HR) have differences in measures of presynaptic dopamine transmission compared to low responders (LR) to a novel environment, including altered dopamine release and behavioral response to indirect dopamine agonists. This study examined the role of three dopamine terminal fields, the nucleus accumbens, striatum, and medial prefrontal cortex, in differences between HR and LR. In the first experiment, dopamine was infused directly into the nucleus accumbens (0, 3, 10, and 30 micrograms/side) or the striatum (0, 10, 30, and 100 micrograms/side). HR showed a greater behavioral response to both the 3 and 30 micrograms/side doses infused into the nucleus accumbens compared to LR. No differences between HR and LR were revealed by dopamine infusion into the striatum. In the second experiment, radioligand binding assays were performed to determine if differences exist between high and low responder rats in the Bmax and/or KD of radiolabeled antagonist ligands for the dopamine D1 and/or D2 receptors. There were fewer D2 binding sites in the nucleus accumbens and fewer sites in the striatum in HR compared to LR. High responders showed a greater Bmax for D1 binding sites in the nucleus accumbens than LR. No differences in number of binding sites for D1 receptors were observed between HR and LR in the striatum. No differences between HR and LR in D2 or D1 receptor binding were observed in the medial prefrontal cortex. There were no differences in KD for any of the dopamine receptors in the regions examined.(ABSTRACT TRUNCATED AT 250 WORDS)