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Sub-chronic Ghrelin Receptor Blockade Attenuates Alcohol- and Amphetamine-Induced Locomotor Stimulation in Mice

Petra Suchankova, Jörgen A. Engel, Elisabet Jerlhag
DOI: http://dx.doi.org/10.1093/alcalc/agv100 121-127 First published online: 31 August 2015


Aims Ghrelin initially emerged as a gut-brain hormone controlling food intake, meal initiation and appetite mainly via hypothalamic circuits in both rodents and humans. The findings that ghrelin receptors (GHS-R1A) are expressed in reward-related areas, including the nucleus accumbens (NAc) and ventral tegmental area (VTA), suggest that ghrelin is a novel reward regulator. Indeed, ghrelin signalling mediates the rewarding and motivational properties of addictive drugs. In addition, daily co-administration of a GHS-R1A antagonist and various addictive drugs prevents the drug-induced locomotor sensitization in rats.

Methods The present series of experiment were designed to evaluate the effect of repeated pharmacological GHS-R1A suppression on drug-induced locomotor stimulation in more detail.

Results We showed that sub-chronic pre-treatment of the GHS-R1A antagonist, JMV2959, attenuated the ability of acute administration of alcohol as well as of amphetamine to stimulate locomotion. However, there was no effect of sub-chronic JMV2959 treatment on locomotor activity per se or on the expression of the GHS-R1A gene (Ghsr) in the VTA or the NAc compared with vehicle treatment. In addition, sub-chronic ghrelin treatment caused a locomotor sensitization.

Conclusions While previous research has pinpointed ghrelin as an appetite regulator the present study together with previous studies suggest that ghrelin signalling modulates various reward-mediated behaviours in rodents. Collectively, this suggests that the GHS-R1A could be a key target for novel treatment strategies for addiction.

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