Cocaine- and amphetamine-regulated transcript peptides play a role in drug abuse and are potential therapeutic targets.
Cocaine- and amphetamine-regulated transcript (CART) peptides (55 to 102 and 62 to 102) are neurotransmitters with important roles in a number of physiologic processes. They have a role in drug abuse by virtue of the fact that they are modulators of mesolimbic function. Key findings supporting a role in drug abuse are as follows. First, high densities of CART-containing nerve terminals are localized in mesolimbic areas. Second, CART 55 to 102 blunts some of the behavioral effects of cocaine and dopamine (DA). This functional antagonism suggests that CART peptides be considered as targets for medications development. Third, CREB in the nucleus accumbens has been shown to have an opposing effect on cocaine self-administration. CREB may activate CART expression in that region, and, if so, CART may mediate at least some of the effects of CREB. Fourth, in addition to the effects of CART on DA, DA can influence CART in the accumbens. Thus a complex interacting circuitry likely exists. Fifth, in humans, CART is altered in the ventral tegmental area of cocaine overdose victims, and a mutation in the CART gene associates with alcoholism. Overall, it is clear that there are functional interactions among CART, DA, and cocaine and that plausible cellular mechanisms exist to explain some of these actions. Future studies will clarify and extend these findings.
Kuhar
Michael J
MJ
Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA. michael.kuhar@emory.edu
Jaworski
Jason N
JN
Hubert
George W
GW
Philpot
Kelly B
KB
Dominguez
Geraldina
G
D000437:Alcoholism / Q000235:genetics / Q000378:metabolism; D000662:Amphetamines / Q000494:pharmacology; D001835:Body Weight / Q000235:genetics; D002460:Cell Line; D003042:Cocaine / Q000009:adverse effects* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology; D004298:Dopamine / Q000494:pharmacology / Q000502:physiology; D018492:Dopamine Antagonists / Q000494:pharmacology; D062787:Drug Overdose; D006728:Hormones / Q000378:metabolism; D007026:Hypothalamic Area, Lateral / Q000378:metabolism; D009411:Nerve Endings / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D009434:Neural Pathways / Q000502:physiology; D009714:Nucleus Accumbens / Q000378:metabolism; D009928:Organ Specificity; D010146:Pain / Q000503:physiopathology; D010446:Peptide Fragments / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D015290:Second Messenger Systems / Q000502:physiology; D019966:Substance-Related Disorders / Q000188:drug therapy / Q000378:metabolism*; D013681:Tegmentum Mesencephali / Q000187:drug effects / Q000378:metabolism; D014158:Transcription, Genetic; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
D000662:Amphetamines; C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D018492:Dopamine Antagonists; D006728:Hormones; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D012333:RNA, Messenger; C507709:cocaine- and amphetamine-regulated transcript peptide (62-102), human; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; C428723:cocaine- and amphetamine-regulated transcript protein (55-102); D000242:Cyclic AMP; D003042:Cocaine; D004298:Dopamine