**1. Introduction**

Milk is a widely consumed, affordable, and highly nutritive food, which serves as a key source of, among others, protein, calcium, potassium, magnesium, and vitamins (especially A and D) in industrialized countries [1–6]. In Western societies, cow's milk (CM) products represent the largest share of dairy available on the market, and cow's skim milk varieties have become common. However, recent years have generated interest in milk from other species, such as goat's milk (GM). The use of GM as an alternative to CM has been driven by the findings in humans and laboratory animals showing potential beneficial nutritive consequences of GM intake and differences in physiological responses to GM or CM consumption, (for review, see [7]). For example, Bellioni-Businco et al. reported that individuals with a CM allergy were able to drink five times more GM than CM before the

symptoms of an allergic response appeared [8]. In studies utilizing rodent models, Barrionuevo et al. demonstrated that GM increases utilization of copper, zinc, and selenium [9]. Bioavailability of iron and copper was found to be improved in GM-fed rodents suffering from malabsorptive syndrome and in healthy controls [9,10]. Finally, GM improved bone turnover in iron-deficient rats compared to rats fed CM [11,12].

Surprisingly, little is known about GM's acceptance and preference relative to the main dairy product in today's food environment in the Western world. There is no systematic analysis of propensity to ingest GM and CM or relative palatability of GM vs. CM in either humans or in laboratory animal models. Consequently, our understanding of acceptance and palatability of GM compared to CM is still mainly based on anecdotal evidence and on market availability, both heavily influenced by local cultural or environmental aspects (such as in Western vs. Asian countries) and habituation-driven intake of a specific milk type [13]. This is a major gap in knowledge as palatability affects, among others, the amount of food eaten in a single meal, the rate of consumption, food anticipation, and satiety. It has a profound effect on activity of brain circuits responsible for processing energy intake (including the hypothalamus (HYP) and brain stem (BS)) and reward (such as the nucleus accumbens; NAcc) [14–16]. These parameters can, in turn, impact a plethora of mechanisms outside the central nervous system (CNS), via neural and hormonal interactions linking the brain and peripheral tissues [17–19].

Here, we present for the first time a comprehensive investigation of short-term intake and palatability profiles of GM and CM in laboratory rodent models (mice and rats) using skim milks. We report consumption data on the acceptance (no-choice) and preference (choice) scenarios of calorie-matched milks and milk-enriched solid diets. Consumption data are accompanied by the analysis of expression of appetite-related genes in the HYP and BS, two brain regions predominantly involved in energy balance control, and in the NAcc, a key site that regulates eating for palatability [15,16]. We examined mRNA levels of genes involved in promoting consumption, such as those encoding neuropeptide Y (NPY), Agouti-related protein (AgRP), ghrelin receptor, orexin, opioid peptides/receptors, and gap junction protein, connexin 36 (Cx36). The analysis also included transcripts related to decreased appetite and termination of consumption, such as oxytocin, melanocortin receptors 3 (MC3R) and 4 (MC4R), and proopiomelanocortin (POMC). Typically, presentation of tastants that differ in palatability and composition, among other traits, evokes some changes in expression within this subset of genes, reflecting a different propensity of an animal to ingest specific diets [16,20]. A number of physiological functions by the brain vary with age, including appetite. Weight is typically gained throughout early and middle age, followed by gradual, age-associated anorexia. In line with that, a drive to consume food (and responsiveness to palatability) is high during the earlier stages of life, whereas in aged animals, anhedonia and decreased responsiveness to rewarding diets and to drugs that promote eating for pleasure ensue (e.g., see [21–23]). Therefore, in our feeding experiments, we studied rodents that belong to three distinct age groups: adolescents, adults, and aged animals. It should also be noted that rats and most mammals, other than select groups of humans, poorly digest lactose post-weaning. Though lactase activity in adult rats is residual, rats fed as much as 30% lactose in their daily diet from post-weaning to day 98 had normal body growth or body weight course (their body weight was somewhat lower) [24]. Taking it into consideration, however, in this current study we focused on short-term rather than long-term exposure to milk or milk containing chow.
