Augmentation of cocaine hyperactivity in rats by systemic ghrelin

The alcohol-induced locomotor stimulation and accumbal dopamine release is suppressed in ghrelin knockout mice

“…A role of ghrelin in reward induced by other addictive drugs has also been shown. Thus, systemic ghrelin enhances cocaine-induced locomotor stimulation as well as condition place preference in rats and high serum levels of ghrelin is associated with cocaine-seeking behaviour in rats (Wellman et al, 2005;Davis et al, 2007;Tessari et al, 2007). Moreover, GHS-1A antagonism attenuates the amphetamine-and cocaine-induced locomotor simulation, accumbal dopamine release and condition place preference in mice (Jerlhag et al, 2010b).…”

The role of the central ghrelin system in reward from food and chemical drugs

“…Indeed, SNPs and haplotypes of both the pro-ghrelin and GHS-R1A genes have been associated with increased weight in alcohol dependent individuals (Landgren et al 2008). Central ghrelin signalling has over the last years been shown to mediate the reward from alcohol Jerlhag et al 2010b), cocaine, amphetamine (Jerlhag et al 2010a;Wellman et al 2005;Tessari et al 2007), and palatable/rewarding food Perello et al 2010;Skibicka et al 2011a;Skibicka et al 2011b). Collectively these studies imply that central ghrelin signalling, including the GHS-R1A may constitute a novel target for development of treatment strategies for addictive behaviours.…”

“…When consumed in excess and over time food can cause the same brain neuroadaptations as drug abuse (Grigson 2002). Indeed, human imaging studies show that there is an underlying disruption in the reward systems in the brain (Holden 2001;Potenza et al 2003;, as well as in brain regions important for inhibitory control The identification of the reward circuits as a key target for ghrelin has therefore led to the unexpected discovery that the central ghrelin signalling system is required for reward induced by addictive drugs aur and Ryabinin 2010;Tessari et al 2007;Wellman et al 2005) as well as palatable food Perello et al 2010;Skibicka et al 2011a;Skibicka et al 2011b). The ghrelin receptor, GHS-R1A, has emerged therefore as a relevant therapeutic target for addictive behaviours.…”

“…Moreover, the effect of ghrelin is more pronounced in rodents exposed to alcohol since peripheral ghrelin administration to alcohol naïve rats only slightly increases the alcohol intake (Lyons et al 2008). Additionally, ghrelin augments cocaine-induced reward as measured by locomotor activity and conditioned place preference, and elevated ghrelin levels are associated with cocaine-seeking in rats (Davis et al 2007;Tessari et al 2007;Wellman et al 2005). Food restriction, that increases ghrelin levels (Gualillo et al 2002), augments cocaine-as well as amphetamine-induced locomotor stimulation, enhances cocaineseeking behaviour and increases the self-administration of cocaine or amphetamine in rats (Carroll et al 1979).…”

Peripherally Circulating Ghrelin Does Not Mediate Alcohol‐Induced Reward and Alcohol Intake in Rodents

“…The findings that the cholinergic–dopaminergic reward link is activated by pharmacological‐induced hyperghrelinemia (Jerlhag, 2008; Jerlhag et al., 2012) and that elevated ghrelin levels associated with craving (Addolorato et al., 2006; Koopmann et al., 2012; Leggio et al., 2012), may imply that high plasma levels of ghrelin may be needed for reward interactions. Supportively, animal studies show that hyperghrelinemia is associated with cocaine seeking and that peripheral ghrelin administration augments the cocaine‐induced conditioned place preference and locomotor stimulation (Clifford et al., 2012; Davis et al., 2007; Tessari et al., 2007; Wellman et al., 2005, 2012). Conclusively, future studies on the role of peripheral versus central ghrelin in relation to alcohol reward, intake, and craving are warranted.…”