A genetic epilepsy rat model displays endophenotypes of psychosis.
The incidence of psychosis is increased in people with epilepsy, including idiopathic generalized epilepsies. To study the biological basis for this co-morbidity, we compared GAERS, a genetic rat model of absence epilepsy, to non-epileptic control rats (NEC). Mature, 14-week old GAERS showed enhanced amphetamine-induced locomotor hyperactivity - a feature also present in young (6-week old) GAERS prior to epilepsy onset. Prepulse inhibition and its disruption by psychotropic drugs did not differ between strains, although GAERS displayed elevated startle responses at both epileptic and pre-epileptic ages. The frontoparietal cortex of GAERS displayed a twofold increase in the power of gamma (30-80 Hz) oscillations, a proposed neurophysiological correlate of psychosis. Radioligand binding autoradiography demonstrated reduced densities of dopamine transporters in the caudate nucleus and nucleus accumbens core and of dopamine D2 receptors in the caudate nucleus. GAERS provide an opportunity to study the neurodevelopmental, genetic and therapeutic aspects of psychiatric comorbidities associated with epilepsy.
Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne, VIC, Australia. ncjones@unimelb.edu.au
Nigel C
NC
Jones
Sally
S
Martin
Ika
I
Megatia
Tahir
T
Hakami
Michael R
MR
Salzberg
Didier
D
Pinault
Margaret J
MJ
Morris
Terence J
TJ
O'Brien
Maarten
M
van den Buuse
D000818:Animals; D015897:Comorbidity; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage; D004777:Environment; D004827:Epilepsy / Q000235:genetics* / Q000378:metabolism / Q000523:psychology*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006185:Habituation, Psychophysiologic / Q000502:physiology; D006948:Hyperkinesis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D008297:Male; D010641:Phenotype; D011618:Psychotic Disorders / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar; D013045:Species Specificity
D018765:Dopamine Uptake Inhibitors