Taste Hedonics and the Intake of Alcohol and Food

Abstract: This thesis includes four papers based on animal experimental work. They analyze the way in which activation of a specific motivational state - hunger- modulates the rewarding actions of alcohol and taste palatability. In Paper I it was shown that a reduction of body weight to 80% of normal was associated with a significant increase in 6% ethanol drinking in the rat. Two subsequent experiment indicated that adrenal activation contributed to the food restriction-induced enhancement of alcohol drinking. Adrenalectomized rats showed no evidence of enhanced alcohol drinking during food restriction and treatment with the enzyme inhibitor cyanoketone, which blocks stress-induced basal corticosterone secretion, partly prevented the food restriction-induced increase in ethanol drinking. Paper II tested the hypothesis that chronic food restriction, which was found in Paper I to enhance the voluntary intake of ethanol, is accompanied by positive alliesthesia for the taste of alcohol. Do food restricted rats perceive the taste of ethanol as more pleasant than animals with ad lib access to food? It was found that two weeks of food restriction, which approximately doubled the voluntary intake of ethanol, was associated with a significant increase in the hedonic response elicited by intraoral infusions of ethanol. In a following experiment we used metyrapone as a tool to assess the importance of adrenal corticosterone secretion for the increased palatability of alcohol observed during food restriction. Attenuation of corticosterone synthesis by this enzyme inhibitor significantly reduced the hedonic taste reactions to alcohol observed in food restricted rats; this reduction in alcohol taste reward was accompanied by a non-significant increase in the aversive reaction to alcohol. Given the 'food-like' properties of alcohol Paper III examined the hypothesis that benzodiazepine exposure not only enhances the intake and palatability of food but also promotes the ingestion and taste pleasure derived from ethanol. Does benzodiazepine exposure induce positive alliesthesia to ethanol? We first examined the effect of the benzodiazepine, midazolam, on the consumption of 6% ethanol. It was found that midazolam increased home cage ethanol drinking. Another intake experiment, in which ethanol was infused directly into the oral cavity through an indwelling catheter, also showed that midazolam stimulated alcohol ingestion. The affective responses to intraoral infusions of ethanol was subsequently monitored in benzodiazepine-treated rats. Taste reactivity testing showed that midazolam significantly increased the occurrence of hedonic orofacial responses and suppressed the number of passive drippings. A similar response pattern was observed following administration of diazepam and chlordiazepoxide. The increased hedonic response to ethanol induced by midazolam was attenuated by pretreatment with the benzodiazepine receptor antagonist flumazenil, the latter drug exerting no effects on its own. This suggests that benzodiazepines may increase ethanol's taste hedonic properties by acting as positive allosteric modulators on GABA-A receptors. Paper IV examined whether the parabrachial nucleus mediates the enhancement of palatability following benzodiazepine exposure. The taste reactivity paradigm was used to measure affective reactions elicited by a bittersweet solution (7 % sucrose and 0.01 % quinine). Food intake (cereal mash) was measured after brainstem microinjections of midazolam into the parabrachial nucleus, the nucleus of the solitary tract, the pedunculopontine tegmental nucleus, or the 4th ventricle, and affective reactions to sucrose/quinine were also measured after microinjections of midazolam into the parabrachial nucleus. Midazolam dose dependently increased food intake and enhanced positive affective taste reactivity patterns to the bittersweet solution when microinjections were delivered to the parabrachial nucleus. When administered to the other brainstem sites these doses of midazolam had no effect. We therefore conclude that the parabrachial nucleus can mediate benzodiazepine-induced enhancement of the hedonic impact of taste as well as mediating enhancement of eating behavior. Key words: Alcohol drinking, Adrenalectomy, Corticosterone, Cyanoketone, Food intake, Food restriction, GABA, Metyrapone, Taste reactivity, Benzodiazepine, Chlordiazepoxide, Cis(Z)-flupentixol, Diazepam, Flumazenil, Microinjections, Midazolam, Nucleus of the Solitary tract, Palatability, Parabrachial nucleus, Peduculopontine Tegmental Nucleus, Reward, 4th ventricle. Anna Söderpalm, Department of Psychology, Göteborg University, Box 500, 405 30 Göteborg, Sweden. E-mail: [email protected]