Do metabolic signals stimulate intake in rat pups? Susan E. Swithers * Department of Psychological Sciences, Purdue University, 703 Third Street, West Lafayette, IN 47907-2004, USA Received 17 January 2003; accepted 17 January 2003 Abstract During early postnatal life, rat pups make a transition from suckling to food intake independent of the dam. Accompanying this transition is the requirement for pups to independently modulate their ingestive behavior. In adult animals, one set of signals known to modulate intake is generated by administration of agents that interfere with metabolism of glucose or fats (such as mercaptoacetate [MA] or 2-deoxyglucose [2-DG]). However, demonstrations of the effects of such agents in young rats have been less robust. Recent work in our lab has focused on examining the effects of MA and methyl palmoxirate (MP) on independent ingestion in pre- and periweaning rats. In rat pups between the ages of 12 and 15 days, latencies to initiate intake independent of the dam are typically longer relative to older or younger pups. However, the latency with which 12- and 15-day-old pups initiate independent ingestion is reduced following administration of MA. Further, MA produces physiological changes consistent with a change in the oxidation of fatty acids in 12- and 15-day-old pups, and similar physiological changes are produced during moderate periods of food deprivation in pups at the same ages. Thus, signals related to changes in the oxidation of fatty acids normally produced by moderate food deprivation in periweaning rats may provide a fundamental signal involved in the onset and modulation of intake independent of the dam. D 2003 Elsevier Science Inc. All rights reserved. Keywords: Rats; Mercaptoacetate; 2-Deoxyglucose; Fats During the first postnatal weeks, rat pups make a transition from obtaining food and fluids exclusively from the dam through suckling to independently acquiring and consuming food away from the context of suckling. This transition represents a critical juncture for the pup, as failure to navigate the transition has potentially profound conse- quences (e.g. starvation or dehydration). Physiological sig- nals, which guide transitional ingestive behavior, may be highly specialized and differ from those observed in older animals. In fact, work on the controls of independent ingestive behavior during the preweaning period in rats has suggested that during the early postnatal period mech- anisms and systems related to the modulation of intake are specialized and different from those observed in adults. For example, the principal diet of rat pups, dam’s milk, derives 60–70% of its calories from lipids, and young rat pups preferentially use fat-derived ketone bodies over glucose for metabolic fuels [1–3]. Reliance on fat as a metabolic energy source declines gradually throughout the pre- and postwean- ing period, with reliance on ketone bodies decreasing as pups approach transition through weaning (e.g. Refs. [4,5]). In addition, levels of gluconeogenesis are also substantially higher in rat pups compared with adults, decreasing in magnitude during the preweaning period [6]. Thus, physio- logical processes related to energy utilization differ signific- antly in neonatal rats compared with adults. Likewise, modulation of intake in young rat pups (6 days of age or less) is different from modulation of intake in adult rats. In young rats, independent ingestion (i.e. intake of a diet away from the dam and the suckling context) can be stimulated by dehydration ([7], although see Ref. [8]), while adult rats display dehydration anorexia [9,10]. Further, in young pups, independent intake after a period of deprivation appears to be modulated only by hydrational signals, not metabolic or caloric signals. For example, when 6-day-old pups are given gastric infusions during a deprivation period, infusions that are purely hydrational and infusions that provide both calories and hydration have equivalent effects on subsequent intake [11]. Consistent with a minimal role for signals other than dehydration in the modulation of 0031-9384/03/$ – see front matter D 2003 Elsevier Science Inc. All rights reserved. doi:10.1016/S0031-9384(03)00106-9 * Tel.: +1-765-494-6279; fax: +1-765-496-1264. E-mail address: swithers@psych.purdue.edu (S.E. Swithers). Physiology & Behavior 79 (2003) 71 – 78