S.L Dickson, C. Cook, S.M.Luckman, E Schele
Presented at Neuroscience 2017 Washington DC, USA
Feelings of hunger carry a negative valence (emotion) signal that appears to be conveyed through agouti-related peptide (AgRP) neurons in the hypothalamic arcuate nucleus1. The circulating hunger hormone, ghrelin, activates these neurons although it remains unclear whether it also carries a negative-valence signal. Given that ghrelin also activates pathways in the midbrain that are important for reward, it remains possible that ghrelin could act as a positive reinforcer and hence, carry a positive-valence signal. Here we used condition preference/avoidance tests to explore the reinforcing/aversive properties of ghrelin, delivered by intracerebroventricular (ICV) injection (2 µg/injection once a day for 4 days). We found that ICV ghrelin conditioned avoidance, both in a conditioned place preference/avoidance test (CPP/CPA, in which the animals avoid a chamber previously paired to ghrelin injection) and in a conditioned ﬂavor preference/avoidance test (CFP/CFA, in which the animals consume/avoid a taste previously paired to ghrelin injection). These effects of ghrelin to induce a CPA were observed when conditioning to ghrelin occurred in the absence of food (77% reduction in time spent in ghrelin-paired compartment, P<0.001) and presence of food (in this case an 82% reduction; P<0.001). We did not ﬁnd evidence, however, that brain ghrelin delivery to rats induces malaise (in the pica test). After conditioning, the preference for the ﬂavor that had been conditioned to ICV ghrelin injection (31 ± 7 %) was dramatically reduced by over half (P < 0.001) compared with the initial preference (71 ± 3 %), which was determined prior to conditioning. Our data indicate that ICV ghrelin carries a negative-valence signal consistent with its role as a circulating hunger hormone and with its effects to activate AgRP neurones
1 Betley JN et al., Nature. 2015 521:180-5.