title: Behavioral impairments in rats with chronic epilepsy suggest comorbidity between epilepsy and attention deficit/hyperactivity disorder.
abstract: Attention deficit/hyperactivity disorder (ADHD) is encountered among patients with epilepsy at a significantly higher rate than in the general population. Mechanisms of epilepsy-ADHD comorbidity remain largely unknown. We investigated whether a model of chronic epilepsy in rats produces signs of ADHD, and thus, whether it can be used for studying mechanisms of this comorbidity. Epilepsy was induced in male Wistar rats via pilocarpine status epilepticus. Half of the animals exhibited chronic ADHD-like abnormalities, particularly increased impulsivity and diminished attention in the lateralized reaction-time task. These impairments correlated with the suppressed noradrenergic transmission in locus coeruleus outputs. The other half of animals exhibited depressive behavior in the forced swimming test congruently with the diminished serotonergic transmission in raphe nucleus outputs. Attention deficit/hyperactivity disorder and depressive behavior appeared mutually exclusive. Therefore, the pilocarpine model of epilepsy affords a system for reproducing and studying mechanisms of comorbidity between epilepsy and both ADHD and/or depression.
authors.affiliation: Department of Pediatrics, David Geffen School of Medicine at UCLA, USA.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Pineda
authors.affiliation: Department of Psychology, David Geffen School of Medicine at UCLA, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, USA.
authors.forename: J David
authors.initials: JD
authors.lastname: Jentsch
authors.affiliation: Department of Pediatrics, David Geffen School of Medicine at UCLA, USA.
authors.forename: Don
authors.initials: D
authors.lastname: Shin
authors.affiliation: Department of Neurosurgery, David Geffen School of Medicine at UCLA, USA.
authors.forename: Grace
authors.initials: G
authors.lastname: Griesbach
authors.affiliation: Department of Pediatrics, David Geffen School of Medicine at UCLA, USA; Department of Neurology, David Geffen School of Medicine at UCLA, USA; UCLA Children's Discovery and Innovation Institute, USA.
authors.forename: Raman
authors.initials: R
authors.lastname: Sankar
authors.affiliation: Department of Pediatrics, David Geffen School of Medicine at UCLA, USA; UCLA Children's Discovery and Innovation Institute, USA. Electronic address: mazarati@ucla.edu.
authors.forename: Andrey
authors.initials: A
authors.lastname: Mazarati
mesh_terms: D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000139:chemically induced / Q000150:complications* / Q000473:pathology; D001526:Behavioral Symptoms / Q000209:etiology*; D001921:Brain / Q000378:metabolism; D002908:Chronic Disease; D003192:Compulsive Behavior / Q000139:chemically induced; D003292:Convulsants / Q000633:toxicity; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced / Q000150:complications* / Q000473:pathology; D007839:Functional Laterality / Q000187:drug effects; D046353:Immobility Response, Tonic / Q000187:drug effects; D018021:Lithium Chloride / Q000633:toxicity; D008297:Male; D010775:Photic Stimulation; D010862:Pilocarpine / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D013550:Swimming / Q000523:psychology
chemical_list: D003292:Convulsants; D010862:Pilocarpine; D018021:Lithium Chloride
keywords: 5-HT; ADHD; Attention deficit/hyperactivity disorder; Depression; EPMT; Epilepsy; FCV; FST; LC; LRTT; Lateralized reaction-time task; NE; Norepinephrine; PFC; RN; SE; Serotonin; TLE; attention deficit/hyperactivity disorder; elevated plus maze test; fast cyclic voltammetry; forced swimming test; lateralized reaction-time task; locus coeruleus; norepinephrine; prefrontal cortex; raphe nucleus; serotonin; status epilepticus; temporal lobe epilepsy