ABSTRACT
HIROKO TOGASHIl-*, KEN-ICHI UENO l, TAKU YAMAGUCHIl, MACHIKO MATSUMOTO \ KASANE HIGUCHI2, HIDEYA SAITO3 and MITSUHIRO YOSHIOKA l 1 Department of Neuropharmacology, Hokkaido University Graduate School of Medicine Kita-15, Nishi-7, Kita-ku, Sapporo 060-8638, Japan
2 Department of Oral Science Function, Hokkaido University Graduate School of Dental Medicine, Kita-15, Nishi-7, Kita-ku, Sapporo 060-8638, Japan
3 Department of Basic Sciences, Japanese Red Cross Hokkaido College of Nursing, Kitami 090-0011, Japan
Abstract-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
*To whom correspondence should be addressed. E-mail: thiro@med.hokudai.ac.jp
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.
