In addition to changes in BDNF-related gene function, we also found alterations of several other important transcripts in the NAc (Fig. 7). We see elevations in Gria2, the transcript encoding the GluR2 subunit of the AMPA glutamate receptor, in animals treated with both cocaine and antibiotics. Previous studies have shown that cocaine induction of GluR2 in this brain region is downstream of the transcription factor ∆FosB, and that overexpression of GluR2 in the NAc increased behavioral responses to low doses of cocaine, similar to effects seen in our animals52. Additionally, increased surface expression of AMPA glutamate receptor subunits is seen in animals expressing behavioral sensitization after prolonged periods of withdrawal53. In addition to elevations in the Gria2 transcript, animals treated with antibiotics and cocaine showed a significant elevation in Drd1, the transcript encoding the D1 dopamine receptor. Signaling via D1 dopamine receptors is known to be crucial for the reward mechanisms underlying cocaine abuse5455. Additionally, activity of the NAc medium-spiny neurons expressing these receptors is crucial for the formation of both locomotor sensitization and conditioned place preference5657. While the current
