In vivo basal and amphetamine-induced striatal dopamine and metabolite levels are similar in the spontaneously hypertensive, Wistar-Kyoto and Sprague-Dawley male rats.
Nigrostriatal alterations are proposed to partially underlie the hypertension and hyperactivity exhibited by the spontaneously hypertensive rat (SHR). Here, in vivo microdialysis was used to measure baseline and d-amphetamine (AMPH)-stimulated striatal dopamine (DA) and metabolite levels in adult male SHR, Wistar-Kyoto (WKY), and Sprague-Dawley (SD) rats. At approximately 19 weeks of age, baseline levels of DA, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) were measured after which time, each rat was injected intraperitoneally with 2 mg/kg AMPH and samples were collected for the subsequent 200 min. There were no significant strain differences in baseline levels of DA, HVA, and 5-HIAA. The baseline level of DOPAC was decreased in the WKY relative to the SD. AMPH treatment altered DA, DOPAC, HVA, and 5-HIAA to a similar extent in all strains; thus, there were no significant strain differences, nor did the area under the curve (AUC) for DA levels differ between strains. AUC for DOPAC was significantly smaller for the WKY relative to the SD strain, likely due to the lower baseline level. At the single dose of amphetamine used here, the results indicate that in vivo DA levels in the SHR are similar to the WKY and SD strains.
HFT-132, Division of Neurotoxicology, National Center for Toxicological Research/FDA, 3900 NCTR Road, Jefferson, AR 72079, USA. sferguson@nctr.fda.gov
Sherry A
SA
Ferguson
Bobby J
BJ
Gough
Amy M
AM
Cada
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003913:Dextroamphetamine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
D015259:Dopamine Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D006897:Hydroxyindoleacetic Acid; D003913:Dextroamphetamine; D004298:Dopamine; D006719:Homovanillic Acid