Baseline behavior, but not sensitivity to stimulant drugs, differs among spontaneously hypertensive, Wistar-Kyoto, and Sprague-Dawley rat strains.
Deficits in temporal processing are implicated in Attention Deficit Hyperactivity Disorder (ADHD) for which the most common rodent model is the Spontaneously Hypertensive Rat (SHR). To assess strain differences in temporal processing, males and females of the SHR, Wistar-Kyoto (WKY), and Sprague-Dawley (SD) strains were compared on two timing tasks: one requiring maintenance of a lever press for 10-14 s (TRD, temporal response differentiation) and the other requiring withholding of a lever press for 10-14 s (DRL, differential reinforcement of low rates). Performance of the progressive ratio (PR) task more directly assessed food-motivated behavior. Strains did not differ in task acquisition; however, steady state TRD and DRL performance of the SHR and WKY strains was less accurate which was related to increased burst (non-timing related) responses in those strains relative to the SD. PR performance demonstrated that the SHR and WKY strains exhibited higher response rates and breakpoints than the SD. Subsequently, methylphenidate (1, 3.25, 4.50, 7.50, and 12.0 mg/kg) and d-amphetamine (0.1, 0.25, 0.65, 1.0, and 2.0 mg/kg) were administered intraperitoneally pre-testing. Both drugs disrupted TRD and DRL performances by increasing burst response frequency; however, the strains were not differentially sensitive to either drug. Strain differences were generally maintained throughout the drug and extinction portions of the study. These results indicate increased similarity between the SHR and WKY strains relative to the SD in performance of timing and motivation tasks. Further, the current results do not support continued use of the SHR as a model for ADHD.
Ferguson
Sherry A
SA
Division of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, AR 72079, USA. Sherry.Ferguson@fda.hhs.gov
Paule
Merle G
MG
Cada
Amy
A
Fogle
C Matthew
CM
Gray
Erika P
EP
Berry
Kimberly J
KJ
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D003913:Dextroamphetamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D013045:Species Specificity
D000697:Central Nervous System Stimulants; D008774:Methylphenidate; D003913:Dextroamphetamine