DEVELOPMENTAL DIFFERENCES IN DOPAMINE SYNTHESIS INHIBITION BY (+ -)-7-OH-DPAT/

Dopamine synthesis modulation by the D(2-)family agonist (+/-))-7-OH-D PAT was explored in striatum, accumbens, and prefrontal cortex of 10-4 0 day old rats using the gamma-butyrolactone (GBL) autoreceptor model. GBL produced an age-dependent increase in dopamine synthesis that was inhibited by (+/-) 7-OH-DPAT (0.1-13.5 mg/kg) at all ages and antagon ized by eticlopride in the nucleus accumbens and striatum. The ID50 of (+/-) 7-OH-DPAT increased with age, suggesting decreased autoreceptor sensitivity with maturation. In prefrontal cortex, (+/-) 7-OH-DPAT in hibited synthesis between 10-30 days, with no evidence of autoreceptor function at 40 days. Dopamine synthesis was also inhibited with the D -3/D-2 agonist quinpirole at 15 days of age in vivo and yielded simila r results to those obtained with (+/-) 7-OH-DPAT. Finally, under condi tions that result in low D-2 receptor affinity, D-3 specificity was ex amined in vitro at 15 days with (+/-) 7-OH-DPAT, which produced compar able (yet more potent) effects to these observed in vivo. These findin gs illustrate D-3 autoreceptor-like activity in ascending dopamine reg ions and provide further support for transient prefrontal cortex autor eceptor-like function that recedes by puberty.