Non-selective attention and nitric oxide in putative animal models of Attention-Deficit Hyperactivity Disorder

Abstract

Non-selective attention (NSA) to environmental stimuli has been measured in putative animal models of Attention-Deficit Hyperactivity Disorder (ADHD), such as the Spontaneously Hypertensive (SHR) and the Naples High-Excitability (NHE) rat lines. A series of experiments has been carried out on male juvenile SHR and Wistar-Kyoto (WKY) controls (experiment 1) and on the NHE and two controls, i.e. the Naples Low-Excitability (NLE) and a random-bred (NRB) line (experiment 2). It was done under basal conditions or following a single injection of the nitric oxide synthase (NOS) inhibitor L-nitro-arginine-methylester (L-NAME: 0.1-10 mg/kg, i.p.), or vehicle, 30 min before testing on day 1 and vehicle alone before testing on days 2 and 3 in SHR/WKY (experiment 3) and the Naples lines (experiment 4). The behavior in a Lát maze during three consecutive 10-min exposures at 24-h intervals was monitored by a CCD video camera and analyzed off-line for frequency and duration of rearings on hindlimbs per 1-min blocks. The results demonstrated that both SHR and NHE rats showed a higher frequency of rearings of shorter duration than controls. With time of testing, the duration of rearings tended to increase in the WKY but not the SHR. In the Naples lines the duration tended to increase in all but mostly in the NHE rats. The acute inhibition of NOS by L-NAME significantly increased the duration of rearing episodes both in SHR and NHE rats only at 10 mg/kg in the second part of the testing period. Therefore, NSA, as indexed by the duration of rearings, is defective in both hyperactivity models against different genetic backgrounds. In addition, this impairment is dependent upon nitric oxide (NO), which appears to play a significant role in these processes.