Anxiety-related behavior in juvenile stroke-prone spontaneously hypertensive rats — an animal model of attention-deficit/hyperactivity disorder

Attention-deficit/hyperactivity disorder (AD/HD) is defined as a developmental disorder, manifested by deficit sustained attention (inattention), and/or hyperactivity-motor impulsiveness. Neuropsychological evidence indicates the comorbidity of anxiety disorder with AD/HD. The aim of the present study was to characterize anxiety-related behavior of the juvenile stroke-prone spontaneously hypertensive rat (SHRSP), an animal model of AD/HD, and compare with genetic and/or normotensive controls. Our hypothesis, that low susceptibility to fear/anxiety stimuli might underlie impulsive behavior in juvenile SHRSP, was assessed by a contextually conditioned fear paradigm. In order to examine whether contextual fear stimuli would affect the synaptic efficacy in the hippocampus, changes in field potentials of perforant path-dentate gyrus (DG) synapses were recorded in the freely behaving rat. Aversive footshock (FS) stimuli elicited intense freezing behavior in genetic and/or normotensive controls. Re-exposing to the FS chamber in the 30-min retention period also produced freezing behavior, as contextually conditioned fear response, in genetic and/or normotensive controls. In contrast, SHRSP exhibited a significant attenuation in freezing behavior both in the 5-min post FS period (immediately after FS) and in the 30-min retention period (24 hours after FS) as compared to genetic and/or normotensive controls. Pain perception as measures of behavioral responses to electric FS, jumping and/or vocalization, indicated that less anxiety-related response in SHRSP did not simply result from low susceptibility to FS stimuli. During the re-exposure to contextual fear stimuli, SHRSP and a normotensive control rat exhibited a decrease in the amplitude of the evoked population spikes in perforant path-DG synapses, accompanying freezing behavior. The synaptic response in this hippocampal subfield was mimicked by low frequency stimulation (1 Hz). These synaptic responses induced by behavioral and electrophysiological manipulations, freezing and LFS, were less pronounced in SHRSP than those in the control. Our findings indicate that the impaired responsiveness to contextually conditioned fear stimuli, less anxiety-related freezing behavior, in juvenile SHRSP, might explain the impulsive behavior in this AD/HD animal model.