The effects of FG 7142 on sensory-specific satiety in rats

Abstract

Three experiments used intake, clusters, and licks per cluster to study the effects of the GABA inverse agonist, FG 7142, on sensory-specific satiety in rats. In Experiment 1, rats were offered one of two palatable solutions and 30 min later tested with the same or the other solution. Rats that received the same solution consumed less, exhibited fewer clusters, fewer licks per cluster and a more rapid decline in rate of licking than rats tested with the other solution. In Experiments 2 and 3, rats tested with the same solution under FG 7142 showed fewer clusters and fewer licks per cluster than vehicle rats. Rats tested with the other solution under FG 7142 showed fewer licks per cluster but more clusters than vehicle rats. The results were discussed in terms of the distinction between “liking” and “wanting” and the role of GABA in the former but not the latter.

Introduction

Offered a choice between two equally palatable and familiar foods, one of which has been ingested to satiety, laboratory subjects select the other food for further ingestion. The sensory properties of the ingested food are said to have undergone satiety. Sensory-specific satiety is well documented. It has been observed in subjects from various animal species, including people, when they choose between any of a range of recently ingested foods and a relatively novel one, and when they choose between two foods identical in terms of their micronutrient (e.g., fat or protein) composition but differing in their flavor. Sensory-specific satiety is one of the mechanisms by which a diet containing different foods increases ingestion relative to one lacking that variety. Hence, it may be a contributor to the prevalence of obesity in a society where a range of high-calorie and high-fat foods are relatively cheap and readily available. Sensory-specific satiety may also be one of the mechanisms by which omnivores solved the problem of obtaining adequate nutrition from a range of different foods. This satiety could bias selection and ingestion of other foods in advance of complete metabolic satiety and, hence, allows extraction of nutrients from these other foods.

A food subjected to sensory-specific satiety does not just elicit less ingestion: such a food is also impaired in its ability to act as a reward for instrumental responses and as an unconditioned stimulus (US) for Pavlovian conditioned responses [6]. Indeed, the devaluation of a food by pre-feeding is a standard technique used to assess the role of response–reward or conditioned stimulus (CS)–US associations in the control of instrumental and Pavlovian responses [1], [2]. Moreover, a recently ingested food also loses its ability to elicit oro-facial responses indicative of “liking”. Taste reactivity measures in rats have shown that an oral infusion of a recently ingested flavor elicits less positive ingestive reactions (tongue protrusions, paw licking) than does infusion of a different flavor [3], [13]. This decline in hedonics is transient, with its peak occurring in the period shortly after ingestion [10], [16]. A recently ingested food elicits few, if any, aversive reactions (e.g., headshake, gaping) and does not produce an aversion to that food, indicating that ingestion produces a transient reduction in oro-facial responses indicative of liking. Such findings have led to the view that a recently ingested food suffers a transient loss in hedonics. This loss suppresses further ingestion of that food and promotes the selection of a different food whose palatability is largely intact.

GABA plays a critical role in the regulation of feeding behaviour [12], [14]. Drugs, e.g., benzodiazepines, which facilitate activity at the GABA A receptor site, stimulate feeding in both deprived and non-deprived rats. This stimulation is likely due to the effects of these drugs on food hedonics as they increase both the preference for palatable solutions (e.g., sucrose) over water and the liking reactions elicited by an oral infusion of a palatable solution. Conversely, inverse agonists – which reduce activity at this site – depress ingestion of palatable food. For example, FG 7142 (N-methyl-β-carboline-3-carboxymide) reduces intake [8] and the duration of feeding bouts [4]. This effect of FG 7142 on ingestion is thus likely due to a reduction in food hedonics, but to the best of our knowledge, this remains unknown. Moreover, this effect of FG 7142 was observed in rats exposed to a single palatable food, but, again to the best of our knowledge, the effects of the drug have not been assessed in a sensory-satiety paradigm where the palatability of one but not another food has been reduced.

The present experiments studied the effects of FG 7142 on the hedonic responses to a palatable solution that has or has not been recently ingested. As noted, ingestive responses (e.g., tongue protrusions and paw licking) to an orally infused solution are one measure of positive hedonics. Another measure can be obtained from the distribution of licking responses to a solution. Licks are generated in bursts separated by pauses whose duration is used to form sequences and reveal the number of licking ‘bouts’ or clusters that occur across a meal [5]. The size and number of these lick clusters provide an index of hedonics [5], [7]. For example, increased concentrations of sucrose produce corresponding increases in the number of bursts and hence in the size of the clusters [5] whereas bitter tasting solutions decrease cluster size [17]. We used this measure of hedonics. In three experiments, rats drank one of two palatable, familiar solutions and were then offered the same or the other solution. The aim of Experiment 1 was to demonstrate sensory-specific satiety. More specifically, the aim was to show that rats drank less of the same solution and exhibited fewer clusters than they did of the other solution, and that they reduced licking more rapidly to the same than the other solution. Experiments 2 and 3 followed the initial drinking bout with an injection of either FG 7142 or vehicle in order to assess the effects of the drug on intake and the size of the clusters elicited by subsequent exposure to the recently ingested or the relatively novel solution. We expected that rats injected with FG 7142 would drink less of the other solution and show fewer clusters than rats injected with vehicle, that is, we expected the drug to reduce intake and the hedonic reactions elicited by the relatively novel solution.