CART Peptides and Drugs of Abuse: A Review of Recent Progress

Abstract

Earlier studies suggesting an involvement of cocaine and amphetamine regulated transcript peptide (CARTp) in the actions of drugs of abuse are confirmed in the most recent publications. This seems especially true for the psychostimulants where CARTp in the nucleus accumbens inhibits or regulates the actions of these drugs; the regulation is lost after repeated drug use which may be an important mechanism in addiction. The other drugs, including nicotine, alcohol, opiates, and perhaps caffeine can affect CARTp or CART mRNA levels. While the exact mechanism is not always clear, the hope is that these findings may provide some insight for the development of medications. While binding studies indicate the existence of specific G-protein coupled receptors (GPCR) receptors for CARTp, major work to be done is the cloning of these receptors.

CART peptide in the nucleus accumbens regulates psychostimulants: Correlations between psychostimulant and CART peptide effects

“…Previous work in the NAc indicated that CART peptide had an average inhibitory effect, and that this inhibition tended to regulate the maximal activity of the PS- or DA-induced behavioral effects; for reviews see (Rogge et al, 2008; Zhang et al, 2012; Subhedar et al, 2014; Kuhar, 2016). But in this study, we considered and included the individual responses in the analysis.…”

“…Cocaine-and-Amphetamine-Regulated-Transcript peptide (CART 55-102, CART peptide) is an active substance/neurotransmitter with a variety of effects throughout the body (Rogge et al, 2008; Zhang et al, 2012; Subhedar et al, 2014; Kuhar, 2016). In the brain, CART mRNA and peptides are found in many discrete nuclei including the nucleus accumbens (NAc), a region with a strong dopamine (DA) input (Douglass et al, 1995; Koylu et al, 1998), and exposure to cocaine (COC) or amphetamine (AMPH) increases the levels of CART mRNA in the NAc (Douglass et al, 1995; Albertson et al, 2004).…”

“…Also, PS-induced effects were altered in CART knockout mice (Couceyro et al, 2005), though not all studies agree (Moffett et al, 2006). More recent findings have been reviewed (Kuhar, 2016). …”

CART Peptide Regulates Psychostimulant-Induced Activity and Exhibits a Rate Dependency

“…These include feeding and body weight, depression and anxiety, stress, hormonal control, psychostimulant (PS) action [2,3,4,5,6,7,8], and others. With regard to PS action, CART peptides appear to regulate the action of cocaine, amphetamine, and dopamine.…”

“…With regard to PS action, CART peptides appear to regulate the action of cocaine, amphetamine, and dopamine. Injection of CART peptide (CART55-102) into the nucleus accumbens (NAc) reduces the average effect of PSs on locomotor activity (LMA) and cocaine-induced reward [2,3,4,5,6,7,8,9]. …”