Enhanced apomorphine sensitivity and increased binding of dopamine D ₂ receptors in nucleus accumbens in prepubertal rats after neonatal blockade of the dopamine D₃ receptors by (+)-S14297

The role of dopamine (DA) D₃ receptors is controversial in early developmental stages of specially locomotor activity. Past studies have only tested behavioral changes induced by neonatal administration of nonselective dopamine antagonist such as haloperidol or sulpiride in adult rats. We investigated the role of neonatal blockade of DA D₃ receptors at (postnatal day, P1 to P12) using the DA D₃ receptor antagonist (+)-S14297 on paradigms related to DA behaviors including locomotor activity in novel environment and after administration of the DA nonspecific agonists d-amphetamine, and apomorphine. Additionally, autoradiographic studies were performed to correlate behavioral alterations with DA D₁-like, D ₂-like, and D₃ receptors. All studies were performed at two critical ages, prepubertal (P35) and postpubertal (P60). The quantitative autoradiogaphic study revealed increases in the expression of DA D ₂-like receptor expression in the nucleus accumbens (NAcc) in prepubertal animals that received the DA D₃ antagonist (+)-S14297 at neonatal age. In addition, novel environment and apomorphine administration (0.5 mg/kg, s.c.), induced increases of locomotor activity in prepubertal animals that received the DA D₃ antagonist (+)-S14297. Autoradiographic and behavioral results suggest that blockade of DA D₃ receptors after birth may mediate different neurodevelopmental aspects of the dopaminergic pathway before and after puberty.