A threshold neurotoxic amphetamine exposure inhibits parietal cortex expression of synaptic plasticity-related genes

Abstract

Compulsive drug abuse has been conceptualized as a behavioral state where behavioral stimuli override normal decision making. Clinical studies of methamphetamine users have detailed decision making changes and imaging studies have found altered metabolism and activation in the parietal cortex. To examine the molecular effects of amphetamine on the parietal cortex, gene expression responses to amphetamine challenge (7.5mg/kg) were examined in the parietal cortex of rats pretreated for nine days with either saline, non-neurotoxic AMPH, or neurotoxic AMPH dosing regimens. The neurotoxic AMPH exposure [3 doses of 7.5 mg/kg/day AMPH (6 hr between doses), for nine days] produced histological signs of neurotoxicity in the parietal cortex while a nonneurotoxic dosing regimen (2.0 mg/kg/day × 3) did not. Neurotoxic AMPH pretreatment resulted in significantly diminished AMPH challenge-induced mRNA increases of activity-regulated cytoskeletal protein (ARC), nerve growth-factor inducible protein A (NGFI-A), and nerve growthfactor inducible protein B (NGFI-B) in the parietal cortex while neither saline pretreatment nor nonneurotoxic AMPH pretreatment did. This effect was specific to these genes as tissue plasminogen activator (t-PA), neuropeptide Y (NPY) and c-jun expression in response to AMPH challenge was unaltered or enhanced by amphetamine pretreatements. In the striatum, there were no differences between saline, neurotoxic AMPH, and non-neurotoxic AMPH pretreatments on ARC, NGFI-A or NGFI-B expression elicited by the AMPH challenge. These data indicate that the responsiveness of synaptic plasticity related genes are sensitive to disruption specifically in the parietal cortex by threshold neurotoxic AMPH exposures.

The Retinal Proteome in Experimental Diabetic Retinopathy

“…Quantitative PCR analysis was performed as described previously (26). Briefly quantitative PCR was performed using the 7900HT Sequence Detection System (Applied Biosystems, Foster City, CA), 384-well optical plates, and Assay-On-Demand (Applied Biosystems) gene-specific primers and probes.…”

Persistent Alterations in Mesolimbic Gene Expression with Abstinence from Cocaine Self-Administration

“…RNA quantity and quality were assessed using the Agilent 2100 Bioanalyzer with the RNA 6000 Nano Assay (Agilent, Palo Alto, CA). cDNA synthesis and qPCR were performed as previously described (Bowyer et al, 2007). qPCR on samples used the 7900HT Sequence Detection System (Applied Biosystems, Foster City, CA), 384-well optical plates, and Assay-OnDemand (Applied Biosystems) gene-specific primers and probes (Maley et al, 2004).…”

“…A full listing of genes, gene names, and assay identification numbers is given in Supplementary Table 1. Relative quantities were calculated using ABI SDS 2.2.2 RQ software and the 2 ÀDDCt analysis method (Bowyer et al, 2007;Livak and Schmittgen, 2001) with GAPDH as the endogenous control. GAPDH levels had been determined in preliminary absolute quantitation experiments to be unchanged with cocaine self-administration or forced abstinence (data not shown).…”

Psychostimulant Abuse and Neuroinflammation: Emerging Evidence of Their Interconnection

“…The preponderance of research in the area of stimulant-induced neurotoxicity has focused on oxidative stress and glutamate/dopamine excitotoxicity (Cadet et al 2007;Yamamoto et al 2010). There is also evidence of involvement of changes in synaptic plasticity genes (Bowyer et al 2007) and apoptotic mechanisms (Cadet et al 2001) in psychostimulant toxicity associated with doses sufficient to produce histological evidence of toxicity. However, more recent work indicates that psychostimulant drugs are also able to activate specific components of the innate immune response (IIR), following both acute and chronic psychostimulant exposure (Yamamoto et al 2010).…”