Nancy K. Dess

Selective breeding for differential saccharin intake as an animal model of drug abuse.

A positive relationship between the consumption of sweetened dietary substances (e.g. saccharin and sucrose) and drug abuse has been reported in both the human and other animal literature. The proposed genetic contribution to this relationship has been based on evidence from behavioral, neurobiological, and linkage studies in heterogeneous and homogeneous animal populations. Initial work in several laboratories indicated that rodents that are selected for high alcohol consumption also display an increased preference for sweets compared with low alcohol-consuming animals. More recently, Sprague–Dawley rats have been selectively bred based on high saccharin (HiS) or low saccharin (LoS) consumption, and these lines represent an ideal opportunity to determine whether a reciprocal genetic relationship exists between the consumption of sweetened substances and self-administration of drugs of abuse. The purpose of this review is to examine a series of studies on the HiS and LoS rats for drug-seeking and drug-taking behavior using laboratory animal models that represent critical phases of drug abuse in humans. The data support the hypothesis that sweet consumption and drug self-administration are closely related and genetically influenced. Other characteristics of HiS and LoS rats are discussed as possible mediators of the genetic differences such as activity, impulsivity, novelty reactivity, stress, and emotionality. The interaction of sweet preference with biological variables related to drug abuse, such as age, sex, and hormonal influences, was considered, as they may be additive vulnerability factors with consumption of sweet substances. In the studies that are discussed, the HiS and LoS lines emerge as ideal addiction-prone and addiction-resistant models, respectively, with vulnerability or resilience factors that will inform prevention and treatment strategies for drug abuse.

Ethanol consumption in rats selectively bred for differential saccharin intake.

Rat lines selectively bred for high ethanol consumption consume more saccharin solution than do their low-ethanol-consuming counterparts. The present study utilized the technique of reciprocal selection to examine the reliability of the saccharin/ethanol relationship; specifically, consumption of 1-10% ethanol solution was measured in rats selectively bred for high vs. low saccharin consumption (Occidental HiS and LoS lines). HiS rats consumed more ethanol than did LoS rats. These results support the idea that individual differences in ethanol and saccharin consumption share some common mechanism(s).

The bitter with the sweet: The taste/stress/temperament nexus

Is the tongue a window to the psyche? In rats, stress alters taste, and individual differences in taste are related to measures of emotion. The present study concerned stress-induced changes in taste and its modulation by temperament in people. College students rated saccharins bitterness and sweetness and a tones loudness after exposure to a mild stressor. Temperament (trait arousability, pleasure, and dominance) was assessed separately. When individual differences were ignored, stress appeared to selectively increase sensitivity to saccharins bitterness. However, the stressors impact was modulated by temperament: Stress nonselectively augmented stimulus magnitude ratings among highly arousable individuals; relative to high-pleasure counterparts, low-pleasure individuals gave higher bitterness ratings and lower sweetness ratings after stress. Taste does seem to provide a glimpse of the emotional life of humans and other animals and opens new avenues to the study of the biological bases of affect.

Stressors in the learned helplessness paradigm: Effects on body weight and conditioned taste aversion in rats

Changes in body weight and taste aversion in the learned helplessness paradigm were examined. In Experiment 1, adult male Sprague-Dawley rats drank saccharin or a control solution, followed by either 100 inescapable shocks or simple restraint. Rats were weighted daily and were tested for saccharin aversion two days after the stress session. Shocked rats gained less weight in the days after stress than restrained controls. Saccharin aversion was apparent only among rats that had consumed saccharin before the stress session. Experiment 2 examined whether control over shock affected body weight or taste aversion. Home-cage controls were included to assess the effects of restraint alone. In addition, the combined effects of shock and a toxin on aversion were studied. Rats drank saccharin solution, followed by escapable or inescapable shock, restraint, or no treatment. Then half of each group was injected with saline; the other half was injected with lithium chloride. As in Experiment 1, shock reduced body weight relative to restraint or no treatment, and shock produced a taste aversion among saline-treated rats. However, shock attenuated the aversion produced by lithium chloride, as did simple restraint. There were no differences in body weight or taste aversion between escapably and inescapably shocked rats. These results suggest a role for stress in the anorexia and weight loss associated with clinical depression and may have implications for theories of learning and learned helplessness.

Taste and emotionality in rats selectively bred for high versus low saccharin intake

Rats were selectively bred for high versus low saccharin ingestion, a putative measure of enhanced stress and emotionality (Dess, 1991). In Experiment 1, third-generation Occidental high-saccharin (HiS) and low-saccharin (LoS) rats were tested for saccharin ingestion and emotionality. The saccharin test confirmed that the lines differed on the selection phenotype. In addition, LoS rats were more emotional, as evidenced by longer emergence latencies and more defecation in a modified open-field test. In Experiment 2, LoS rats had lower quinine preference scores and drank saccharin-adulterated glucose less avidly. These outcomes are reminiscent of the behavior shown by inescapably shocked rats. Unlike helpless rats, however, LoS rats drank less avidly during a dilute sucrose test, an effect more reminiscent of chronic mild stress. The lines did not differ reliably on intake of concentrated glucose or Polycose, even when the latter was mixed with saccharin. In Experiment 3, LoS rats preferred saccharin less strongly than did HiS rats at concentrations of 0.05% to 0.7% and had an aversion to a 1.0% solution. In Experiment 4, LoS rats were affected more by shock, as assessed by stress-induced anorexia. These and other recent findings support the notion of shared mechanisms for taste, emotionality, and stress vulnerability.

Divergent responses to saccharin vs. sucrose availability after stress in rats

Rats were exposed to 100 5-s inescapable, unpredictable shocks then had access to water and saccharin or sucrose solution for 5-6 days. Shock reduced daily drinking during saccharin tests (Experiments 1, 2B, 4) and increased daily drinking during sucrose tests (Experiment 2B). In addition, shock reduced body weight when saccharin, but not when sucrose, was available (Experiments 1, 2B). The specificity of the reductions to saccharin tests (Experiments 2B, 4), equal intake of flavors shortly after stress (Experiments 2B to 4), and failure of saccharin-naive and saccharin-familiar groups to differ (Experiment 3) argue against a neophobia interpretation. Normal or above-normal drinking during sucrose (Experiment 2B) or water-only (Experiment 4) tests indicate an absence of general hedonic, motoric, or hydrational deficits. Qualitative differences in the tastes of saccharin and sucrose may underlie their disparate effects on drinking after shock. Whatever the mechanisms, the present results show that even a severe stressor can decrease or increase ingestion, depending on the flavors available.

Individual differences in vulnerability to inescapable shock in rats.

The present study determined whether individual differences in neophobia during an open-field pretest predict vulnerability to inescapable electric shock, as measured by 2 tests of learned helplessness in rats. Shuttle-escape latencies and saccharin finickiness increased across groups that had received increasing numbers of inescapable shocks 24 hr earlier. Dispersion in the test measure as well as the percentage of variance explained by pretest neophobia were greater when no or few shocks were delivered in the interpolated stress phase. Pretest neophobia was positively related to stress vulnerability in both tests under these conditions. Further increments in stressor severity overwhelmed even the most stress-resistant rats, thereby decreasing dispersion in the test measure and eliminating the predictive value of pretest neophobia. This pattern of outcomes was more robust for the shuttle-escape measure of helplessness.

Individual differences in taste, body weight, and depression in the “helplessness” rat model and in humans

The helplessness paradigm is used extensively in basic stress research and is an experimental model of clinical depression. In Experiment 1, exposure to unsignaled, inescapable shock resulted in finickiness about drinking a weak quinine solution, as previously reported. In contrast, exposure to escapable shock resulted in marked individual differences in finickiness that were predicted by prestress body weight. A more sensitive index of finickiness was used in Experiment 2, and a correlation between body weight and finickiness was observed in nonshocked rats. In Experiment 3, measures of quinine reactivity and body weight predicted depressive symptomatology in a nonclinical human sample. Although research in the helplessness paradigm usually focuses on environmental determinants of distress, the paradigm may help identify and explain individual differences in, or intrinsic modulation of, stress and depression.

Ingestion and emotional health

Evidence abounds of a close relation between ingestive and affective processes in rats and in humans. Emotional distress alters food intake and body weight; conversely, alterations in eating and weight influence emotional health. Thorough experimental analysis of the ingestion-affect relation may clarify the mechanisms of anxiety and depression. A strategy is proposed for examination of environmental and dispositional determinants of ingestive processes, emotionality, and responses to stress.

Responses to basic taste qualities in rats selectively bred for high versus low saccharin intake

Rats selectively bred for relatively high (HiS) and relatively low (LoS) saccharin intake were offered sweet (sucrose), bitter (quinine, sucrose octaacetate), salty (sodium chloride), starchy (Polycose((R))), and sour (citric acid) solutions at several concentrations; sucrose/quinine, and sucrose/citric acid mixtures were also tested. Compared to HiS rats, LoS rats displayed weaker preferences for and lower consumption of sweet, salty, and starchy solutions. HiS and LoS rats did not differ in responses to simple bitter or sour solutions or to adulteration of sucrose with citric acid. However, quinine adulteration reduced sucrose preference more among LoS rats. Thus, selection on a saccharin intake phenotype has yielded line differences on all hedonically positive tastants and, probably as a consequence of that difference, greater finickiness specifically towards bittersweet solutions in the low saccharin-consuming line. Additional work can clarify the psychobiological mechanisms for the phenotypic difference and, potentially, the reasons for its relationship to measures of emotionality.