Vol. 299, Issue 3, 1021-1026, December 2001

Multiple Behavioral Effects of Cocaine- and Amphetamine-Regulated Transcript (CART) Peptides in Mice: CART 42-89 and CART 49-89 Differ in Potency and Activity

Anthony W. Bannon, Jennifer Seda, Michelle Carmouche, Jonathan M. Francis, Mark A. Jarosinski and James Douglass

Amgen Inc., Neuroscience, Thousand Oaks, California (A.W.B., J.S., M.C., J.M.F., J.D.); and Amgen Boulder Inc., Peptide Chemistry, Longmont, Colorado (M.A.J.)

Cocaine- and amphetamine-regulated transcript (CART) encodes a neuropeptide precursor protein that is highly abundant in cells of the hypothalamus. To date, the major research focus into the function of CART peptides has been feeding behavior. However, CART mRNA is found in other areas of the brain as well as some peripheral tissues, suggesting possible broader functions of this peptide. In this study, we investigated the effects of two CART peptides, CART 42-89 and CART 49-89, in several behavioral assays. Peptides were administered by i.c.v. route of administration. Both CART 42-89 and CART 49-89 inhibited food intake with the minimally effective dose of CART 42-89 (0.5 µg) being 5-fold greater than that of CART 49-89 (0.1 µg). Both peptides also produced significant antinociceptive effects in the hot-plate assay with similar potency differences. CART 42-89 significantly inhibited the acoustic startle response (ASR) of pulse alone trials at doses of 0.1 and 0.5 µg. In contrast, CART 49-89 did not affect ASR of pulse alone trials at doses of 0.05 and 0.1 (µg). For prepulse inhibition (PPI) trials, in general, both peptides appeared to enhance the magnitude of PPI and CART 42-89 was less potent than CART 49-89. Overall, these data suggest CART peptides may have multiple roles in central nervous system function and there may be biological differences between two processed forms of CART peptide.