High dose CART peptide induces abnormal EEG activity and behavioral seizures

Cocaine- and amphetamine-regulated transcript (CART) peptides are neurotransmitters found throughout the nervous system and in the periphery. CART has an important role in the regulation of food intake, anxiety, endocrine function, and in mesolimbic-mediated reward and reinforcement. This short report casts light upon previous descriptions of presumed behavioral seizure and tremor activity following administration of CART into the central nervous system. By employing electroencephalographic (EEG) recordings, we document the state of cerebrocortical activity. We find that intracerebroventricular (icv) administration of 5 μg of CART 55–102 readily produces an abnormal EEG characterized initially by high amplitude hypersynchronous alpha in the 8–10 Hz range during behavioral wakefulness as manifest in both cortical and hippocampal theta EEG channels. This reliably progressed in three of three animals tested to unequivocal epileptiform activity accompanied by tremors and assumption of a rigid, tonic body posture. The neural substrates underlying this finding are unclear. This novel description of the epileptogenic quality of CART should lend caution to interpretations of the behaviors attributed to CART in other experimental paradigms.