Repeated amphetamine administration alters the expression of mRNA for AMPA receptor subunits in rat nucleus accumbens and prefrontal cortex

Abstract

Recent evidence suggests that behavioral sensitization to amphetamine is associated with alterations in excitatory amino acid (EAA) transmission in perikarya (ventral tegmental area) and terminal regions (nucleus accumbens [NAc]) of the mesoaccumbens dopamine system. The present study determined whether repeated amphetamine administration alters expression of mRNAs for AMPA receptor subunits. We studied the NAc, because it is the site of expression of amphetamine sensitization, and the prefrontal cortex (PFC), because it is the origin of EAA projections that regulate the mesoaccumbens dopamine system. Rats were treated for 5 days with 5 mg/kg/day amphetamine sulfate or vehicle (controls) and perfused 3 or 14 days after the last injection. We used a novel in situ hybridization method that allows quantification of mRNA levels [Lu et al. (1996) J. Neurosci. Methods, 65:69-76]. Repeated amphetamine administration decreased levels of GluR1 and GluR2 but not GluR3 mRNAs in both core and shell subregions of the NAc at the 14 day withdrawal time; no changes were observed after 3 days of withdrawal. In contrast, levels of GluR1 mRNA in the PFC were increased at 3 but not 14 days of withdrawal, while GluR2 and 3 mRNAs were unchanged. Levels of GluR4 mRNA were very low in both NAc and PFC. Functional properties of heteromeric AMPA receptors are determined by subunit composition. Thus, the observed changes in mRNAs for AMPA receptor subunits may result in altered AMPA transmission in NAc and PFC. This, in turn, may influence the responsiveness of the mesoaccumbens DA system to psychomotor stimulants and potentially contribute to behavioral sensitization.

Acute Amphetamine Exposure Selectively Desensitizes κ-Opioid Receptors in the Nucleus Accumbens

“…In addition, cocaine self-administration produces a postsynaptic decrease in the AMPA receptormediated fEPSP (Schramm-Sapyta et al, 2006). Finally, many studies have demonstrated changes in glutamate receptor subunit levels in the NAc following exposure to either cocaine or amphetamine (Lu et al, 1997 Acute amphetamine alters j-opioid function Y Xia et al Churchill et al, 1999;. How these postsynaptic changes integrate with our observations to alter the function of the circuit remains to be determined.…”

Previous Exposure to Psychostimulants Enhances the Reinstatement of Cocaine Seeking by Nucleus Accumbens AMPA

“…n ¼ 8-9/group. Effect of psychhostimulants on cocaine self-administration N Suto et al protein levels in the NAcc, leaving GluR3 and GluR4 protein levels unchanged (Lu et al, 1997;Lu and Wolf, 1999). On the other hand, exposure to cocaine 17-90 days earlier has been reported to either slightly increase GluR1 (Churchill et al, 1999;Scheggi et al, 2002;Lu et al, 2003) and GluR2 protein levels, leave GluR1 (Fitzgerald et al, 1996;Ghasemzadeh et al, 1999) and GluR2 (Fitzgerald et al, 1996;Churchill et al, 1999;Ghasemzadeh et al, 1999;Scheggi et al, 2002) protein and mRNA levels unchanged and decrease GluR3 and GluR4 mRNA levels (Ghasemzadeh et al, 1999).…”

Homers regulate drug-induced neuroplasticity: Implications for addiction

“…Whether or not the more modest effects of amphetamine regimens upon corticoaccumbens glutamate relate to the duration of withdrawal remains to be determined. In support of this possibility, reductions in the mRNA or protein expression of the AMPA receptor subunits GluR1 and GluR2, and the obligatory NMDA subunit NR1 within the NAC are observed at 14 days withdrawal, but not at earlier time-points [278][279][280][281]. In contrast, changes in glutamate receptor subunit expression are apparent within the PFC during early withdrawal [278][279][280][281][282].…”