Gene expression profiling in the striatum of amphetamine-treated spontaneously hypertensive rats which showed amphetamine conditioned place preference and self-administration

摘要

Attention-deficit/hyperactivity disorder (ADHD), the most commonly diagnosed neurobehavioral disorder of childhood, is usually treated with psychostimulants (e.g., amphetamine). Little is known about the neuronal and behavioral consequences of chronic amphetamine use or abuse in individuals with ADHD. Of all ADHD animal models, the spontaneously hypertensive rat (SHR) is the most validated and widely used. Here, we analyzed striatal transcriptomes in amphetamine-pretreated SHRs (5 mg/kg, i.p. for 7 days [ twice daily]), which showed a conditioned place preference to and self-administration of amphetamine. Microarray analyses revealed increased mRNA expression of 55 genes (>1.65-fold increase), while 17 genes were downregulated (<0.6-fold) in the striatum of SHRs. The main functional categories over-represented among the differentially expressed genes in the striatum include those involved in transcription (e.g., Cebpb, Per2), genes associated with angiogenesis (e.g., Kdr, Klf5), cell adhesion (e.g., Col11a1, Ctgf), apoptosis (e.g., Nfkbia, Perp) and neuronal development (e.g., Egr2, Nr4a3). In conclusion, we dissected the striatal transcriptional responses to the reinforcing effects of repeated amphetamine treatment in the SHR model of ADHD. Future studies should determine the influence of these altered transcripts on amphetamine reinforcement in amphetamine-treated SHRs, and the clinical relevance of the present findings with regard to amphetamine use/abuse in ADHD individuals.