Cocaine exposure during the early postnatal period diminishes medial frontal cortex Gs coupling to dopamine D1-like receptors in adult rat.

The effect of cocaine exposure during early postnatal ages on coupling of dopamine (DA) D(1)- and D(2)-like receptors to their respective Gs/olf and Gi was examined in striatum and medial frontal cortex (MFC). Sprague-Dawley rats were subcutaneously injected with either 50 mg/kg cocaine or vehicle during postnatal day (PnD) 11-20 and dopaminergic D(1)- and D(2)-like receptor signaling was evaluated at PnD 60. Results showed that cocaine exposure did not affect the magnitude of both DA D(1)- and D(2)-like receptor coupling to their respective Gs/olf and Gi in striatum. However, in the medial frontal cortex, the basal and the DA D(1)-like receptor and Gs association were reduced in cocaine-exposed brains. However, there was no change in basal or DA D(2)-like receptor-Gi linkage in medial frontal cortex. Since frontal cortex plays a critical role in regulating cognition and working memory, disruption of DA-modulated circuits or alteration of dopaminergic activity resulting from postnatal cocaine exposure may result in abnormal responses to environmental challenges leading to long-term behavioral changes.