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Vagal Afferents Mediate Early Satiation and Prevent Flavour Avoidance Learning in Response to Intraperitoneally Infused Exendin‐4
Author(s) -
Labouesse M. A.,
Stadlbauer U.,
Weber E.,
Arnold M.,
Langhans W.,
PachecoLópez G.
Publication year - 2012
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/j.1365-2826.2012.02364.x
Subject(s) - medicine , endocrinology , nucleus accumbens , amygdala , lateral parabrachial nucleus , sham feeding , central nucleus of the amygdala , inhibitory postsynaptic potential , dorsal motor nucleus , chemistry , solitary nucleus , parabrachial nucleus , receptor , central nervous system , vagus nerve , secretion , stimulation
Glucagon‐like peptide‐1 receptor ( GLP ‐1R) agonists such as exendin‐4 ( E x‐4) affect eating and metabolism and are potential candidates for treating obesity and type II diabetes. In the present study, we tested whether vagal afferents mediate the eating‐inhibitory and avoidance‐inducing effects of E x‐4. Subdiaphragmatic vagal deafferentation ( SDA ) blunted the short‐term (< 1 h) but not long‐term eating‐inhibitory effect of i.p.‐infused E x‐4 (0.1 μg/kg) in rats. A dose of 1 μg/kg E x‐4 reduced 0.5, 1, 2 and 4 h cumulative food intake in SDA and s ham‐operated rats to a similar extent. Paradoxically, SDA but not s ham rats developed a conditioned flavour avoidance ( CFA ) after i.p. E x‐4 (0.1 μg/kg). SDA completely blunted the induction of c‐ F os expression by E x‐4 in the hypothalamic paraventricular nucleus. E x‐4, however, increased the number of c‐ F os expressing cells, independent of intact vagal afferents, in the nucleus accumbens and in the central nucleus of the amygdala, the lateral external parabrachial nucleus, the caudal ventrolateral medulla and the dorsal vagal complex. These data suggest that intact vagal afferents are only necessary for the full expression of the early satiating effect of E x‐4 but not for later eating‐inhibitory actions, when circulating E x‐4 might reach the brain via the circulation. Our data also dissociate the satiating and avoidance‐inducing effects of the low E x‐4 dose tested under our conditions and suggest that vagal afferent signalling may protect against the development of CFA . Taken together, these findings reveal a complex role of vagal afferents in mediating the effects of GLP ‐1 R activation on ingestive behaviour.