Wake promoting effects of cocaine and amphetamine-regulated transcript (CART)☆

Cocaine- and amphetamine-regulated transcript (CART) peptides modulate anxiety, food intake, endocrine function, and mesolimbic dopamine related reward and reinforcement. Each of these disparate behaviors takes place during the state of wakefulness. Here, we identify a potential wake promoting role of CART by characterizing its effects upon sleep/wake architecture in rats. Dose-dependent increases in wake were documented following intracerebroventricular CART 55–102 administered at the beginning of the rat’s major sleep period. Sustained wake was observed for up to 4h following delivery of 2.0μg of CART peptide. The wake promoting effect was specific to active CART 55–102 because no effect on sleep/wake was observed with the inactive form of the peptide. Increased wake was followed by robust rebound in NREM and REM sleep that extended well into the subsequent lights-off, or typical wake period, of the rat. These findings point to a potential novel role for CART in regulating wakefulness.