Lamotrigine ameliorates seizures and psychiatric comorbidity in a rat model of spontaneous absence epilepsy

• Published in: Epilepsia (Copenhagen) Vol. 53; no. 11; pp. 2005 - 2014
• Main Authors: Huang, Hsin-Yi, Lee, Hsiao-Wei, Chen, Shang-Der, Shaw, Fu-Zen
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.11.2012; Wiley-Blackwell
• Subjects: Absence epilepsy; Animal models; Animals; Anticonvulsants - therapeutic use; Anticonvulsants. Antiepileptics. Antiparkinson agents; Anxiety; Anxiety Disorders - drug therapy; Anxiety Disorders - epidemiology; Anxiety Disorders - psychology; Biological and medical sciences; Comorbidity; Cortex; Depression; Depressive Disorder - drug therapy; Depressive Disorder - epidemiology; Depressive Disorder - psychology; Disease Models, Animal; Epilepsy; Epilepsy, Absence - drug therapy; Epilepsy, Absence - epidemiology; Epilepsy, Absence - psychology; Firing pattern; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Lamotrigine; Long-Evans rat; Male; Medical sciences; Nervous system (semeiology, syndromes); Neurology; Neuropharmacology; Pharmacology. Drug treatments; Random Allocation; Rats; Rats, Long-Evans; Seizures; Seizures - drug therapy; Seizures - epidemiology; Seizures - psychology; Spike-wave discharge; Sucrose; Sugar; Swimming; Triazines - therapeutic use; Mood disorder; Affect affectivity; Animal model; Nervous system diseases; Rat; Absence epilepsy; Epilepsy; Rodentia; Depression; Anticonvulsant; Cerebral disorder; Vertebrata; Mammalia; Convulsion; Long-Evans rat; Animal; Triazine derivatives; Central nervous system disease; Mental disorder; Spike-wave discharge; Spike wave; Anxiety; Neurological disorder; Lamotrigine
• ISSN: 0013-9580; 1528-1167
• DOI: 10.1111/j.1528-1167.2012.03664.x

Summary Purpose:  Lamotrigine (LTG) is an effective clinical treatment for epilepsy associated with absence seizures. However, the impact of LTG administration in studies employing various animal models of epilepsy remains controversial. This study aimed to clarify the outcomes of LTG treatment on absence seizures and comorbid anxiety and depression disorders in Long‐Evans rats with spontaneous spike‐wave discharges (SWDs). Methods:  LTG (10 mg/kg) or water vehicle was chronically administered perorally to Long‐Evans rats (twice daily for 35 days). Cortical activities were recorded to assess the presence of SWDs. Five behavioral tests, including the open field (OF), elevated plus maze (EPM), sucrose consumption (SC), sucrose preference, and forced swimming (FS) tests, were performed after LTG/vehicle treatment. The behavioral indexes of these tests were designed to assess anxiety (OF and EPM tests), depression (SC and FS tests), and preference for hedonistic stimuli (sugar preference test). Key Findings:  Total SWD duration, SWD number, and mean SWD duration were significantly decreased in rats that received 35‐day LTG treatment compared with rats that received vehicle treatment. Rats with spontaneous SWDs versus rats with no SWDs showed significant levels of anxiety and depression in the OF, EPM, and SC tests. Rats with SWDs also showed longer immobility in the FS test. However, the LTG‐treated group compared with the vehicle group presented with significantly lower manifestations of anxiety and depression in the OF, EPM, SC, and sucrose preference tests and shorter immobility in the FS test. Significance:  The results of this study suggest that chronic LTG treatment can benefit patients with epilepsy via suppression of absence seizures and amelioration of comorbid anxiety and depression.