A genetic epilepsy rat model displays endophenotypes of psychosis

Nigel C. Jones, Sally Martin, Ika Megatia, Tahir Hakami, Michael R. Salzberg, Didier Pinault, Margaret J. Morris, Terence J. O'Brien, Maarten van den Buuse

Research output: Contribution to journalArticleResearchpeer-review

43 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)116-125
Number of pages10
JournalNeurobiology of Disease
Volume39
Issue number1
DOIs
Publication statusPublished - Jul 2010

Keywords

  • Dopamine receptor
  • Dopamine transporter
  • GAERS
  • Gamma power
  • Prepulse inhibition
  • Stimulant-induced hyperlocomotor activity

Cite this