lithium-chloride and Feeding-and-Eating-Disorders

Exendin-4 (Ex4), a glucagon-like peptide-1 receptor (GLP-1R) agonist approved to treat type 2 diabetes mellitus, is well known to induce hypophagia in human and animal models. We evaluated the contributions of the hindbrain parabrachial nucleus (PBN) to systemic Ex4-induced hypophagia, as the PBN receives gustatory and visceral afferent relays and descending input from several brain nuclei associated with feeding. Rats with ibotenic-acid lesions targeted to the lateral PBN (PBNx) and sham controls received Ex4 (1 μg/kg) before 24 h home cage chow or 90 min 0.3 M sucrose access tests, and licking microstructure was analyzed to identify components of feeding behavior affected by Ex4. PBN lesion efficacy was confirmed using conditioned taste aversion (CTA) tests. As expected, sham control but not PBNx rats developed a CTA. In sham-lesioned rats, Ex4 reduced chow intake within 4 h of injection and sucrose intake within 90 min. PBNx rats did not show reduced chow or sucrose intake after Ex4 treatment, indicating that the PBN is necessary for Ex4 effects under the conditions tested. In sham-treated rats, Ex4 affected licking microstructure measures associated with hedonic taste evaluation, appetitive behavior, oromotor coordination, and inhibitory postingestive feedback. Licking microstructure responses in PBNx rats after Ex4 treatment were similar to sham-treated rats with the exception of inhibitory postingestive feedback measures. Together, the results suggest that the PBN critically contributes to the hypophagic effects of systemically delivered GLP-1R agonists by enhancing visceral feedback.

Topics: Analysis of Variance; Animals; Antimanic Agents; Appetitive Behavior; Brain Injuries; Eating; Excitatory Amino Acid Agonists; Exenatide; Feeding and Eating Disorders; Glucagon-Like Peptide-1 Receptor; Hypoglycemic Agents; Ibotenic Acid; Lithium Chloride; Male; Parabrachial Nucleus; Peptides; Rats; Rats, Sprague-Dawley; Sucrose; Taste; Venoms; Water Deprivation

In these experiments we examined the effects on gastric motility of cholecystokinin, LiCl, hypertonic NaCl solution, gastric distension, and intraduodenal glucose loads, five dissimilar treatments known to reduce food intake in rats. In addition, we investigated whether any observed effects were dependent on the afferent vagus nerve by pretreating subjects with the neurotoxin capsaicin. Each of the five treatments virtually eliminated the gastric contractions seen after rats had consumed a large meal of chow; these effects were rapid in onset and continued for up to 30 min. The inhibitory effects of cholecystokinin and gastric distension were eliminated by pretreatment with capsaicin, whereas the effects of the other treatments were attenuated only slightly or not at all. Because most of these treatments have been shown to stimulate pituitary oxytocin secretion in rats as well as to inhibit food intake and gastric motility, these results are consistent with the hypothesis that the hypothalamic paraventricular nucleus is a site at which information is integrated in the coordinated control of food intake, gastric function, and neuroendocrine secretion.

Topics: Animals; Anorexia; Capsaicin; Chlorides; Cholecystokinin; Eating; Feeding and Eating Disorders; Gastrointestinal Motility; Glucose; Lithium; Lithium Chloride; Male; Oxytocin; Paraventricular Hypothalamic Nucleus; Rats; Rats, Inbred Strains; Saline Solution, Hypertonic

The study of experimentally induced anorexia poses a problem for investigations of the processes controlling food intake. Inhibition of food consumption may arise from a specific intervention in a physiological system controlling nutritional requirements or from non-specific changes leading to the suppression or contamination of behaviour. The present experiment used the analysis of the structure of behaviour to distinguish between normal anorexia (natural development of satiation) and pathological anorexia brought about by intestinal discomfort (injection of lithium chloride) or adulteration of food (quinine added to diet). The treatments produced marked changes in parameters of feeding and in the frequencies of behaviours associated with eating. Both lithium chloride and quinine treatments gave rise to a slow rate of eating accompanied by a disordered temporal sequence of eating, grooming and resting. This behavioural calibration of anorexia can contribute to the behavioural pharmacology of feeding by helping to diagnose drugs which facilitate normal processes of satiation and those which act via a non-specific disruption of behaviour.

Topics: Animals; Anorexia; Behavior, Animal; Chlorides; Feeding and Eating Disorders; Feeding Behavior; Lithium; Lithium Chloride; Male; Quinine; Rats; Satiation; Satiety Response