Food deprivation and restriction increase the rewarding potency of food, drugs of abuse, and electrical brain stimulation. Based on evidence that the rewarding effects of these stimuli are mediated by the same neuronal circuitry, lateral hypothalamic self-stimulation (LHSS) was used to investigate the involvement of various metabolic signals in the sensitization of reward. In Experiment 1, glucoprivation with @entity897 (150 mg/kg, intraperitoneally (i.p.)) and lipoprivation with @entity1670 (150 mg/kg, subcutaneously (s.c.)), individually and in combination, failed to affect the LHSS threshold in ad lib.-fed @entity35 . These results suggest that signals associated with acute shortage of metabolic substrate do not sensitize reward. Because numerous responses to more prolonged negative energy balance are mediated by @entity10969 ( @entity10969 ), the effect of exogenous @entity10969 upon LHSS was investigated in Experiment 2. Intraventricular infusion of orexigenic @entity10969 doses (2.0, 5.0, and 12.5 g), in ad lib.-fed @entity35 , had no effect on LHSS threshold. In Experiment 3, other concomitants of prolonged negative energy balance--high circulating levels of free @entity1718 (FFA) and @entity4322 (HDB)-were investigated. @entity1670 (250 mg/kg, s.c.), which suppressed serum HDB and FFA levels, had no effect on LHSS in food-restricted or ad lib.-fed @entity35 . @entity15946 (68.4 mg/kg, i.p.), which suppressed serum HDB levels and exacerbated the elevation of FFA levels, also had no effect. Thus, the brain reward system, if modulated by these substances, is not affected by transient, though marked, changes in their levels. To investigate the effect of a sustained increase in levels of FFA and HDB, a "ketogenic" diet was employed. Although this diet produced a fourfold increase in serum HDB levels, it had no effect on LHSS thresholds. Moreover, the failure of @entity15946 (68.4 mg/kg, i.p.) to decrease LHSS thresholds in these @entity35 supports the conclusion that acute shortage of metabolic substrate does not sensitize reward. Other possible mechanisms of reward sensitization, including sustained decreases in circulating insulin and leptin and increases in @entity2819 , are discussed.

A search for the metabolic signal that sensitizes lateral hypothalamic self-stimulation in food-restricted XXXX .

@entity10969 :: ('24604(Tax:10116)', 'Gene') :: ['neuropeptide Y', 'NPY'] @entity15946 :: ('CHEBI:30066', 'Chemical') :: ['Mercaptoacetate', 'mercaptoacetate'] @entity1670 :: ('MESH:D009525', 'Chemical') :: ['Nicotinic acid', 'nicotinic acid'] @entity4322 :: ('MESH:D020155', 'Chemical') :: ['beta-hydroxybutyrate'] @entity2819 :: ('MESH:D003345', 'Chemical') :: ['corticosterone'] @entity35 :: ('10116', 'Species') :: ['rats'] @entity1718 :: ('MESH:D005227', 'Chemical') :: ['fatty acids'] @entity897 :: ('MESH:D003847', 'Chemical') :: ['2-deoxy-d-glucose']
@entity35 :: (10116,Species) :: ['rats']
