title: Regulatory role of the dopamine and norepinephrine transporters in pentylenetetrazol-kindled mice: association with effect of antidepressants.
abstract: In clinical practice, patients with epilepsy are frequently associated with psychiatric disorders, including cognitive impairment, depression, and attention deficit hyperactivity disorder. In fact, patients with epilepsy often take centrally acting drugs, such as antidepressants and anxiolytics; however, it remains unclear whether epilepsy is associated with psychiatric function. The present study examined the effect of kindled epileptic seizures on depression-like behavior in mice. The immobility time of pentylenetetrazol-kindled mice was as long as the immobility time of the controls in both a forced swimming test and a tail suspension test. Bupropion (10mg/kg, i.p.) decreased the duration of immobility in the forced swimming test of pentylenetetrazol-kindled mice, while having no significant effect in controls. Furthermore, atomoxetine (2mg/kg, i.p.) caused a significant decrease in the duration of immobility in the tail suspension test of the pentylenetetrazol-kindled mice, while having no significant effect in controls. Using immunohistochemistry, it was shown that there was no significant change in dopamine transporter levels in the striatum; however, norepinephrine transporter was significantly increased in the perirhinal cortex of the pentylenetetrazol-kindled mice. These results suggested that bupropion (in low doses) and atomoxetine are good candidates for the treatment of patients with epilepsy who suffer from psychiatric symptoms. Furthermore, this mechanism may be involved in the change of norepinephrine transporter expression, at least in the perirhinal cortex.
authors: Department of Medicinal Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8530, Japan.
authors: Kenshi
authors: K
authors: Takechi
authors: Katsuya
authors: K
authors: Suemaru
authors: Hiromu
authors: H
authors: Kawasaki
authors: Hiroaki
authors: H
authors: Araki
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D000069445:Atomoxetine Hydrochloride; D016642:Bupropion / Q000494:pharmacology*; D003863:Depression / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D050483:Dopamine Plasma Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D007696:Kindling, Neurologic / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism; D010433:Pentylenetetrazole; D011437:Propylamines / Q000494:pharmacology*; D012640:Seizures / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D013550:Swimming
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D050484:Norepinephrine Plasma Membrane Transport Proteins; D011437:Propylamines; D016642:Bupropion; D000069445:Atomoxetine Hydrochloride; D010433:Pentylenetetrazole