Non-selective attention in a rat model of hyperactivity and attention deficit: subchronic methylphenydate and nitric oxide synthesis inhibitor treatment

The involvement of dopamine (DA) and nitric oxide (NO) in the process of non-selective attention (NSA) to environmental stimuli has been investigated in the juvenile Spontaneously Hypertensive rat (SHR). To this aim the frequency and duration of rearing episodes in a novelty situation, which is thought to monitor NSA, have been measured in male SHR and Wistar-Kyoto (WKY) control rats following subchronic treatment with methylphenidate (MP; 3 mg/kg) or the nitric oxide synthase (NOS) inhibitor L-Nitro-arginine-methylester (L-NAME; 1 mg/kg) or vehicle daily for two weeks. Different groups were tested at 0.5 h or 24 h after the last injection in a Lat-maze. Tests were repeated twice at a 24 h interval and lasted 10 min each. Upon first exposure, there was a differential drug effect only in the SHR. In fact, MP and L-NAME yielded a shift to the left and to the right, i.e. towards episodes of lower or higher duration, respectively. This shift was more pronounced in the group tested 0.5 h after the last injection. In contrast, both drugs produced a significant lengthening of the rearing episodes in the SM only in comparison with the vehicle-treated rats over days of testing. Therefore both MP and L-NAME appear to shear a similar effect on non-selective attention, although the effect of L-NAME is somewhat paradoxical. The latter is likely to be due to increased arginine selective uptake due to negative feedback with the NO production. The consequent increased arginine availability displaces the NOS inhibitor, thus leading to increased NO production. In conclusion, dopamine and nitric oxide play a role in non-selective attention by synaptic and extrasynaptic mechanisms, respectively, in a rat model of hyperactivity and attention-deficits. (C) 2000 Elsevier Science Ltd. All rights reserved.