Behavioral sensitization to amphetamine is not accompanied by changes in glutamate receptor surface expression in the rat nucleus accumbens

• Published in: Journal of neurochemistry Vol. 109; no. 1; pp. 35 - 51
• Main Authors: Nelson, Christopher L, Milovanovic, Michael, Wetter, Joseph B, Ford, Kerstin A, Wolf, Marina E
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.04.2009; Blackwell Publishing Ltd; Wiley-Blackwell
• Subjects: Addictive behaviors; Adult and adolescent clinical studies; amphetamine; Amphetamine - pharmacology; Amphetamines; Animals; Biochemistry; Biological and medical sciences; Brain; Cell Membrane - drug effects; Cell Membrane - metabolism; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; drug abuse; Drug addiction; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; Male; Medical sciences; Neurology; nucleus accumbens; Nucleus Accumbens - drug effects; Nucleus Accumbens - metabolism; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Rats; Rats, Sprague-Dawley; Receptors, Glutamate - biosynthesis; Rodents; sensitization; Substance Withdrawal Syndrome - metabolism; Vertebrates: nervous system and sense organs; α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor; Drug addiction; Rat; Rodentia; Central nervous system; amphetamine; Basal ganglion; Substance abuse; Activation; Corpus striatum; Glutamate receptor; Subunit; Cell surface; Protein; Encephalon; Nucleus accumbens; Vertebrata; AMPA receptor; Mammalia; Treatment; drug abuse; Sensitization; Intracellular; a-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor; NMDA receptor
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2009.05911.x

We examined whether behavioral sensitization to amphetamine is associated with redistribution of glutamate receptors (GluR) in the rat nucleus accumbens (NAc) or dorsolateral striatum (DLSTR). Following repeated amphetamine treatment and 21 days of withdrawal, surface and intracellular levels of α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) or NMDA receptor subunits were determined using a protein cross-linking assay. In contrast to our previous results in cocaine-sensitized rats, we did not observe redistribution of GluR1 or GluR2 to the cell surface in the NAc after amphetamine withdrawal, although a small increase in total GluR1 was found in the shell subregion. Nor did we observe activation of signaling pathways associated with cocaine-induced AMPA receptor trafficking or changes in NMDA receptor subunits. No significant changes were observed in the DLSTR. We also investigated the effect of administering a challenge injection of amphetamine to amphetamine-sensitized rats 24 h prior to biochemical analysis based on prior studies showing that cocaine challenge decreases AMPA receptor surface expression in the NAc of cocaine-sensitized rats. GluR1 and GluR2 were not significantly altered in either NAc or DLSTR, although a modest effect on GluR3 cannot be ruled out. Our results suggest that glutamate transmission in the NAc is dramatically different in rats sensitized to amphetamine versus cocaine.