Repeated Administration of Amphetamine or Cocaine Does Not Alter AMPA Receptor Subunit Expression in the Rat Midbrain,

Abstract

We previously reported that ventral tegmental area (VTA) dopamine neurons are supersensitive to AMPA when recorded three days after discontinuing repeated amphetamine or cocaine administration. By increasing dopamine cell activity, this may contribute to the induction of behavioral sensitization. The goal of this study was to determine if increased sensitivity to AMPA reflects increased AMPA receptor expression in the midbrain. Immunolabeling for GluR1, GluR2, GluR2/3, and GluR4 was quantified by immunohistochemistry with 35S-labeled secondary antibodies in VTA, substantia nigra, and a transitional area. First, rats were treated for five days with saline or amphetamine (5 mg/kg) and killed three or 14 days after the last injection. No significant changes in immunolabeling were observed for any subunit at either withdrawal time. GluR1 immunolabeling was further examined in rats killed 16-18 hrs or 24 hrs after a single injection of amphetamine or repeated injections of saline, amphetamine (5 mg/kg x 5 days) or cocaine (20 mg/kg x 7 days). No significant differences were observed in any region. Finally, neither repeated amphetamine or cocaine administration significantly altered GluR1 mRNA levels as quantified by reverse transcriptase-polymerase chain reaction. Our results suggest that enhanced responsiveness of VTA dopamine neurons to AMPA after withdrawal from repeated stimulant administration involves mechanisms more complex than increased expression of AMPA receptor subunits.