title: Chronic high fat diet consumption impairs sensorimotor gating in mice.
abstract: Chronic intake of high fat diets (HFD) has been long recognized to induce neuronal adaptations and impair elementary cognitive functions. Yet, the consequences of chronic HFD consumption on central information processing remain elusive. The present study thus explored the impact of chronic HFD consumption on pre-attentive central information processing using the paradigm of prepulse inhibition (PPI) of the acoustic startle reflex in mice. Animals were fed an experimental diet with 60% of its calories derived from fat, and were compared to control low fat diet (LFD, 10% calories from fat) fed animals. A first experimental series demonstrated that adult mice exposed to chronic HFD throughout adolescent development displayed significant deficits in PPI compared to LFD-fed mice. Identical chronic HFD treatment further led to presynaptic dopaminergic abnormalities in the form of increased tyrosine hydroxylase density in the nucleus accumbens core and shell subregions. Moreover, we found that tyrosine hydroxylase density in the nucleus accumbens shell negatively correlated with the mean PPI scores, suggesting a potential contribution of the accumbal dopamine system to HFD-induced PPI deficits. This impression was further supported by an additional series of experiments showing that the HFD-induced attenuation of PPI can be mitigated by systemic administration of the dopamine receptor antagonist haloperidol. Finally, HFD feeding was sufficient to disrupt PPI when its exposure was restricted to the peripubertal period, whilst the same manipulation failed to affect PPI when limited to adulthood. In conclusion, our findings emphasize that pre-attentive information processing as assessed by the PPI paradigm is highly sensitive to nutritional factors in the form of chronic HFD consumption, especially when initiated during peripubertal maturation. It is likely that the disrupting effects of HFD on sensorimotor gating involve, at least in part, dopaminergic mechanisms.
authors.affiliation: Physiology and Behavior Laboratory, Swiss Federal Institute of Technology (ETH) Zurich, Schorenstrasse 16, 8603 Schwerzenbach, Switzerland. Electronic address: marie-labouesse@ethz.ch.
authors.forename: Marie A
authors.initials: MA
authors.lastname: Labouesse
authors.forename: Ulrike
authors.initials: U
authors.lastname: Stadlbauer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Langhans
authors.forename: Urs
authors.initials: U
authors.lastname: Meyer
mesh_terms: D000161:Acoustic Stimulation; D000375:Aging / Q000187:drug effects; D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D004041:Dietary Fats / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D018492:Dopamine Antagonists / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D051379:Mice; D009433:Neural Inhibition / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D055139:Sensory Gating / Q000187:drug effects*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D018492:Dopamine Antagonists; D014446:Tyrosine 3-Monooxygenase; D006220:Haloperidol
keywords: Antipsychotics; Dopamine; High fat diet; Obesity; Prepulse inhibition; Schizophrenia