Role of mesolimbic ghrelin in the acquisition of cocaine reward.

The present study examined the ability of ghrelin administration into either the ventral tegmental area (VTA) or nucleus accumbens (NAc) to potentiate cocaine-induced conditioned place preference (CPP). Additionally, we examined the impact of co-injection of the ghrelin 1a antagonist JMV 2959 with ghrelin in order to evaluate the potential attenuation of ghrelin's effects on cocaine-induced CPP. Adult male Sprague-Dawley rats were allowed simultaneous access to either side of the CPP apparatus to establish baseline chamber preferences. The rats were then restricted to either their non-preferred or preferred side over the course of conditioning which lasted for a total of 8 consecutive days. On days in which rats were restricted to their non-preferred side, systemic cocaine (0.5-5.0 mg/kg IP) followed by central ghrelin (300 pmol), or co-administration of ghrelin (300 pmol) with JMV 2959 (10 µg), was administered either into the VTA or NAc immediately prior to the conditioning period. On alternate days rats were treated with vehicle then placed into what was initially determined to be their preferred side. CPP was calculated as the difference in the percentage of total time spent in the treatment-paired compartment during the post-conditioning session and the pre-conditioning session. Our results indicated that ghrelin potentiated cocaine-induced CPP and that this effect was attenuated by JMV 2959. Overall, these findings provide further evidence that mesolimbic ghrelin signaling is indeed critically involved in mediating the rewarding effects of cocaine.

Microinjection of Ghrelin into the Ventral Tegmental Area Potentiates Cocaine-Induced Conditioned Place Preference.

Prior work has shown that systemic cocaine pretreatment augments cocaine conditioned place preference (CPP) in rats. In contrast, ghrelin receptor antagonism attenuates cocaine and amphetamine-induced CPP. In order to further investigate ghrelin's role in dopamine-mediated reward, the present report examined whether pretreament with ghrelin, administered directly into the ventral tegmental area (VTA) of the midbrain, would potentiate the rewarding properties of cocaine as measured by CPP. Adult male Sprague-Dawley rats were given access to either side of the CPP chamber in order to determine initial side preferences. The rats were then restricted to either their non-preferred or preferred side over the course of conditioning which lasted for a total of 16 consecutive days. This was followed by a final test day to then reassess preference. On days where rats were confined to their non-preferred side, ghrelin (30 - 300 pmol) and cocaine (0.625 - 10 mg/kg IP) were administered immediately prior to the conditioning trial. On alternate days rats were treated with vehicle and placed into what was initially determined to be their preferred side. CPP was calculated as the difference in percentage of total time spent in the treatment-paired compartment during the post-conditioning session and the pre-conditioning session. Our results indicated that both cocaine and ghrelin elicited CPP and that ghrelin pre-treatment potentiated the effect of cocaine on place preference. Overall, these findings provide additional support for the argument that ghrelin signaling within the VTA enhances the rewarding effects of psychostimulant compounds.