Abstract
Methamphetamine (METH) is a widely abused amphetamine analog. Few studies have investigated the molecular effects of METH exposure in adult animals. Herein, we determined the consequences of an injection of METH (10 mg/kg) on transcriptional effects of a second METH (2.5 mg/kg) injection given one month later. We thus measured gene expression by microarray analyses in the nucleus accumbens (NAc) of 4 groups of rats euthanized 2 hours after the second injection: saline-pretreated followed by saline-challenged (SS) or METH-challenged (SM); and METH-pretreated followed by saline-challenged (MS) or METH-challenged (MM). Microarray analyses revealed that METH (2.5 mg/kg) produced acute changes (1.8-fold; P<0.01) in the expression of 412 (352 upregulated, 60 down-regulated) transcripts including cocaine and amphetamine regulated transcript, corticotropin-releasing hormone (Crh), oxytocin (Oxt), and vasopressin (Avp) that were upregulated. Injection of METH (10 mg/kg) altered the expression of 503 (338 upregulated, 165 down-regulated) transcripts measured one month later (MS group). These genes also included Cart and Crh. The MM group showed altered expression of 766 (565 upregulated, 201 down-regulated) transcripts including Avp, Cart, and Crh. The METH-induced increased Crh expression was enhanced in the MM group in comparison to SM and MS groups. Quantitative PCR confirmed the METH-induced changes in mRNA levels. Therefore, a single injection of METH produced long-lasting changes in gene expression in the rodent NAc. The long-term increases in Crh, Cart, and Avp mRNA expression suggest that METH exposure produced prolonged activation of the endogenous stress system. The METH-induced changes in oxytocin expression also suggest the possibility that this neuropeptide might play a significant role in the neuroplastic and affiliative effects of this drug.
Highlights
Methamphetamine (METH) is an indirect agonist that induces the release of dopamine (DA) in brain regions that receive projections from the substantia nigra pars compacta and the ventral tegmental area [1,2,3]
There were no significant differences in DA, dihydroxyphenylacetic acid (DOPAC), or homovanillic acid (HVA) levels between the saline-pretreated and METH-challenged (SM) and METH-pretreated and METHchallenged (MM) groups
The present study shows that an acute METH (2.5 mg/kg) injection can cause differential changes in gene expression in the rat nucleus accumbens (NAc)
Summary
Methamphetamine (METH) is an indirect agonist that induces the release of dopamine (DA) in brain regions that receive projections from the substantia nigra pars compacta and the ventral tegmental area [1,2,3] These brain regions include the nucleus accumbens and the dorsal striatum. Xi et al [3] have shown that a single METH (10 or 20 mg/kg) injection can increase cocaine self-administration measured several days after the METH injection, documenting long-term behavioral effects of the drug They showed that these METH doses impacted the biochemical effects of cocaine in the nucleus accumbens [3]. To our knowledge, there is no study of the long-term effects of single or multiple exposures to the drug on global gene expression in the rat NAc, given the importance of that structure in reward mechanisms [12,13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
