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 overrepresented 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.