Spontaneously hypertensive rats do not predict symptoms of attention-deficit hyperactivity disorder.
The validity of the Spontaneously Hypertensive rat (SHR) as a model for Attention Deficit Hyperactivity Disorder (ADHD) is explored by comparing the SHR with Wistar-Kyoto (WKY) and Wistar rats in a number of different tests. In the open field, SHR are hyperactive compared to both Wistar and WKY, but only at specific ages. At those ages, methylphenidate (1mg/kg) did not attenuate hyperactivity. Subsequently, a dose response study of methylphenidate (0.1-10mg/kg) was conducted in the Differential Reinforcement of Low-rate responding (DRL)-72s and five-choice serial reaction time tests (5-CSRTT). Compared to WKY but not Wistar rats, SHR performed worse on the DRL-72s. Performance was not improved by methylphenidate (0.1-1.0mg/kg). In the 5-CSRTT, attentional performance was similar for all rat strains, but Wistar rats made more impulsive responses than both the SHR and the WKY. Methylphenidate only attenuated impulsivity in Wistar rats. Because SHR do not consistently display symptoms of ADHD across the different tests, and methylphenidate effects were observed in both WKY and Wistar rats, but not in SHR, we conclude that SHR is not a representative animal model for ADHD.
Utrecht Institute for Pharmaceutical Sciences, and Rudolf Magnus Institute of Neuroscience Department of Psychopharmacology, Utrecht University, Sorbonnelaan 16, 3584 CA Utrecht, The Netherlands. F.S.vandenBerg@pharm.uu.nl
Filip S
FS
van den Bergh
Emilie
E
Bloemarts
Johnny S W
JS
Chan
Lucianne
L
Groenink
Berend
B
Olivier
Ronald S
RS
Oosting
D000367:Age Factors; D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy / Q000209:etiology* / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D006973:Hypertension / Q000150:complications* / Q000523:psychology; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D012737:Sex Factors; D013045:Species Specificity
D000697:Central Nervous System Stimulants; D008774:Methylphenidate