Intraperitoneal Administration of CART 55-102 Inhibits Psychostimulant-Induced Locomotion

Abstract

CART (cocaine and amphetamine regulated transcript) peptide functions as both a neurotransmitter and a hormone and is found both in the central nervous system (CNS) and in the periphery. CART peptide in the nucleus accumbens (NAc) has been implicated in the regulation of cocaine-dopamine-mediated locomotion and self-administration, and amphetamine-mediated locomotion and behavior. However, there are no studies on the effect of systemic administration of CART peptide on cocaine and amphetamine-mediated locomotion. In this study, we tested if the systemic administration of CART 55–102 by the intraperitoneal (ip) route has a functional effect on psychostimulant-mediated locomotion in rats as it does when given into the brain. We determined that ip CART 55–102 attenuates psychostimulant-mediated locomotion as it does when administered into the NAc and display a biphasic dose response curve.

Injection of Cocaine-Amphetamine Regulated Transcript (CART) peptide into the nucleus accumbens does not inhibit caffeine-induced locomotor activity: Implications for CART peptide mechanism

“…Our experiments also confirmed that a motor activating dose of caffeine did not alter endogenous CART peptide levels in the NAc, corroborating a previous report (Cho et al , 2015). Our results replicated other results showing that caffeine exerts a biphasic (an inverted ‘U’-shaped) dose-response curve on LMA (Antoniou et al , 1998, Collins et al , 2010, Cook and Beardsley, 2003, El Yacoubi et al , 2000, File et al , 1988, Garrett and Holtzman, 1994, Halldner et al , 2004, Kaplan et al , 1992, Kuzmin et al , 2006, Marin et al , 2011, Powell et al , 2001, Rhoads et al , 2011, Solinas et al , 2002, Svenningsson et al , 1995, Zhang et al , 2011), and buttress other studies that show that intra-NAc CART peptide blunts cocaine-mediated LMA (Jaworski et al , 2003, Job et al , 2012, Job et al , 2014, Job et al , 2013). …”

“…While CART peptide crosses the blood brain barrier and has systemic effects by unknown mechanisms (Job and Kuhar, 2012), we utilized intra-NAc injections to localize the effects of the peptide as mentioned in the Introduction. CART 55-102 was administered via the intra-accumbal route.…”

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

“…Similarly, injections of CART peptide into the ventral pallidum inhibit COC-induced LMA (Hubert et al, 2010). Even injections into the peritoneum can have effects on PS-induced activity (Job and Kuhar, 2012). Without a detailed mechanistic understanding of the CART peptide effect, it is difficult to predict the effect of CART peptide in any given brain region.…”

“…route. In accordance with previous studies (Jaworski et al, 2003; Kim et al, 2003; Jaworski et al, 2008; Job and Kuhar, 2012; Job et al, 2012; Job et al, 2013; Job et al, 2014; Job, 2016), all bilateral intra-NAc and systemic drug and vehicle control injections were given in volumes of 0.5 μL/side and 1 mL/kg, respectively.…”

“…For example, several studies have shown that intra-NAc injections of CART peptide inhibit psychostimulant (PS)- and DA-induced behavioral effects, notably locomotor activity (LMA), and COC self-administration (Jaworski et al, 2003; Kim et al, 2003; Jaworski et al, 2008; Job and Kuhar, 2012; Job et al, 2012; Job et al, 2013; Job et al, 2014; Job, 2016). The bulk of these previous studies on CART peptide-DA interactions have involved an intra-NAc injection of CART peptide followed by other drug treatments and behavioral analyses.…”