Abstract
Recent discoveries indicate an important role for ghrelin in drug and alcohol reward and an ability of ghrelin to regulate mesolimbic dopamine activity. The role of dopamine in novelty seeking, and the association between this trait and drug and alcohol abuse, led us to hypothesize that ghrelin may influence novelty seeking behavior. To test this possibility we applied several complementary rodent models of novelty seeking behavior, i.e. inescapable novelty-induced locomotor activity (NILA), novelty-induced place preference and novel object exploration, in rats subjected to acute ghrelin receptor (growth hormone secretagogue receptor; GHSR) stimulation or blockade. Furthermore we assessed the possible association between polymorphisms in the genes encoding ghrelin and GHSR and novelty seeking behavior in humans. The rodent studies indicate an important role for ghrelin in a wide range of novelty seeking behaviors. Ghrelin-injected rats exhibited a higher preference for a novel environment and increased novel object exploration. Conversely, those with GHSR blockade drastically reduced their preference for a novel environment and displayed decreased NILA. Importantly, the mesolimbic ventral tegmental area selective GHSR blockade was sufficient to reduce the NILA response indicating that the mesolimbic GHSRs might play an important role in the observed novelty responses. Moreover, in untreated animals, a striking positive correlation between NILA and sucrose reward behavior was detected. Two GHSR single nucleotide polymorphisms (SNPs), rs2948694 and rs495225, were significantly associated with the personality trait novelty seeking, as assessed using the Temperament and Character Inventory (TCI), in human subjects. This study provides the first evidence for a role of ghrelin in novelty seeking behavior in animals and humans, and also points to an association between food reward and novelty seeking in rodents.
Highlights
The personality trait novelty seeking describes the response of a person to novel stimuli or situations in terms of tendency to explore, prefer or react positively to the novelty [1]
6) In addition to rodent behavioral studies, we evaluated the association between ten single nucleotide polymorphisms (SNP) in the genes encoding ghrelin (GHRL) and the GHSR and the personality trait novelty seeking in a Caucasian population
The current results extend these findings to include effects of ghrelin onto a behavior closely associated with drug rewardnovelty seeking
Summary
The personality trait novelty seeking describes the response of a person to novel stimuli or situations in terms of tendency to explore, prefer or react positively to the novelty [1]. This trait reliably predicts the tendency to develop drug abuse. While food and drug seeking may be controlled by a partially overlapping mechanism, the relationship between food reward/seeking and novelty seeking behavior is as yet unknown. Considering the rapid rise in obesity, recently suggested to be influenced by pathological food reward behavior, by some even termed ‘‘food addiction’’, the possible relationship between food reward and novelty seeking is worth exploring
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