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Abstract: It is known that microinjection of galanin (GAL) intraventricularly or in specific hypothalamic sites increases food consumption and, conversely, the intake of food increases the expression of GAL in hypothalamic sites. Ethanol (EtOH) is a calorie-rich food as well as a drug of abuse. The research reviewed here shows that GAL may play a similar role in alcohol intake. First, experiments in which GAL was microinjected into the third ventricle or the paraventricular nucleus (PVN) showed increases in EtOH consumption. The increase in EtOH consumption occurred during both the light and dark cycles after GAL injection in the third ventricle in rats with limited EtOH access. Injection of GAL did not increase food intake in rats that had been chronically drinking alcohol. GAL receptor blockade reversed these increases. Microinjection of GAL directly into the PVN also increased ad libitum EtOH intake and blockade of these receptors in the PVN inhibited ad libitum EtOH consumption. Secondly, rats administered EtOH showed increases in GAL in the PVN and related hypothalamic sites. EtOH injection and voluntary intake, both ad libitum and limited access, increased GAL gene and peptide expression in the PVN consistently across administration procedures. These experiments show that GAL injection increases alcohol intake and that the intake of alcohol increases GAL, suggesting a positive feedback relationship between alcohol intake and specific hypothalamic GAL systems. Such a relationship may contribute to the motivation to consume excessive alcoholic beverages and the development of alcohol dependence. [Copyright &y& Elsevier]

Animals and humans are known to overeat on highly palatable and energy dense high-fat foods. To investigate mechanisms that mediate this hyperphagia, an acute “preload-to-test meal” paradigm was used (based on Warwick, 2000), in which normal weight adult Sprague-Dawley rats were given a small high-fat (HF) or low-fat (LF) preload and then, after an intermeal interval (IMI), were allowed to freely consume a subsequent test meal for 30min. Several experiments were performed to determine the robustness of the acute HF-induced hyperphagia and mechanisms that may underlie this phenomenon. In all tests, a HF preload of only 10–15kcal, compared to an equicaloric LF preload, significantly stimulated food intake by 40–50% (4–6kcal) in subsequent test meal. This effect occurred with HF and LF preloads that were liquid or solid, equal in energy density and palatability, ingested or injected, and followed after a 60- or 120-min IMI by a test meal with variable fat content. This robust hyperphagia after HF preload was invariably associated with a 2- to 3-fold increase in circulating levels of triglycerides, with no change in leptin or insulin. It was accompanied by increased expression of galanin in the paraventricular nucleus and orexin in the perifornical hypothalamus, peptides known to stimulate intake on a fat-rich diet. Repeated administration of HF compared to an equicaloric LF preload significantly increased 24-h food intake. These results define an acute paradigm for studying hyperphagia on HF diet under controlled conditions and suggest mechanisms that possibly mediate this phenomenon. Supported by MH43422. [Copyright &y& Elsevier]

Abstract: To investigate mechanisms that mediate the greater food intake induced by a fat-rich diet, the present study tested an acute “preload-to-test meal” paradigm in normal-weight rats. In this paradigm, the rats were given a small high-fat (HF) compared to low-fat (LF) preload and, after an intermeal interval, allowed to consume freely on a subsequent test meal. Modified versions of this paradigm were tested to determine the robustness of the greater caloric intake induced by the HF preload while standardizing the test protocol. A HF preload of 10–15 kcals, compared to an equicaloric LF preload, significantly increased food intake by 40–50% in the subsequent test meal. This effect, a 4–6 kcal increase, was observed with HF preloads equal in energy density and palatability to the LF preloads. It was evident with preloads or test meals that were liquid or solid, preloads that were injected, test meals that had variable fat content, and natural intermeal intervals of 60–120 min. This overeating after a HF preload was invariably associated with a 2- to 3-fold increase in circulating levels of triglycerides (TG), with no change in leptin or insulin. It was also accompanied by increased expression of the orexigenic peptides, galanin in the paraventricular nucleus and orexin in the perifornical lateral hypothalamus. Moreover, if given repeatedly over several days, the HF compared to equicaloric LF preload significantly increased 24-h food intake. These results establish a protocol for studying the phenomenon of increased feeding on a HF diet under controlled conditions and suggest possible underlying mechanisms involving circulating lipids and orexigenic peptides. [Copyright &y& Elsevier]