cp-154526 and Acute-Disease

Studies indicate that adolescence is a time of increased sensitivity to the rewarding effects of nicotine, and that stress is associated with an increased risk for smoking initiation in this age group. It is possible that stress leads to increased nicotine use in adolescence by augmenting its rewarding properties. Corticotropin-releasing factor type 1 receptors (CRF-R1) mediate physiological and behavioral stress responses. They may also mediate stress-induced potentiation of activity in multiple neural substrates implicated in nicotine reward.. The aim of the present study was to determine the effect of acute stressor exposure on single trial nicotine conditioned place preference (CPP) in adolescent male rats using a biased CPP procedure and the role of CRF-R1 in this effect.. A single episode of intermittent footshock administered 24 h before the start of place conditioning dose-dependently facilitated acquisition of CPP to nicotine (0.2, 0.4, and 0.6 mg/kg). Pretreatment with CP-154,526 (20 mg/kg), a selective CRF-R1 antagonist, 30 min before footshock exposure significantly attenuated the effect of prior stress to facilitate nicotine CPP acquisition. CP-154,526 pretreatment had no effect in animals conditioned with a nicotine dose that produced CPP under non-stress conditions, suggesting a specific role for CRF-R1 following stress.. Taken together, the results suggest that during adolescence, nicotine reward is enhanced by recent stressor exposure in a manner that involves signaling at CRF-R1. Information from studies such as this may be used to inform efforts to prevent and treat adolescent nicotine dependence.

Topics: Acute Disease; Age Factors; Animals; Conditioning, Psychological; Dose-Response Relationship, Drug; Male; Nicotine; Pyrimidines; Pyrroles; Rats; Rats, Sprague-Dawley; Receptors, Corticotropin-Releasing Hormone; Stress, Psychological

Hyperglycemia and insulin resistance after surgical stress are mediated by a complex neuroendocrine response. The present studies were undertaken to determine whether a corticotropin releasing factor (CRF)-receptor 1 (R1) antagonist, CP-154,526 (CP) could alter trauma-induced effects on blood glucose levels, insulin action on skeletal muscle, and dexamethasone-induced suppression of endogenous glucocorticoid secretion.. We used a standardized experimental model of small intestinal resection in the rat. Studies were performed 2 hours after surgery in four groups of rats (n = 24-48) given vehicle or 40 mg of CP i.p. 1 hour before surgical trauma or only anesthesia (controls). Measurements of (I) b-glucose and p-insulin, corticosterone, and ACTH; (II) glucose transport; (III) phosphatidylinositol 3-kinase (PI 3-K) activity in skeletal muscle; and (IV) the dexamethasone-suppression test were performed.. Surgery resulted in hyperglycemia, reduced insulin-stimulated glucose transport, and a pathological dexamethasone-suppression test. B-glucose levels were attenuated in traumatized rats given CP compared to vehicle (P < 0.05). After surgery, p-corticosterone levels were moderately reduced by CP (P < 0.05) and p-ACTH unchanged by the drug. Glucose transport and PI 3-kinase activity as well as the dexamethasone-suppression test were unaffected by administration of CP.. Hyperglycemia in response to small intestinal resection in the rat could be reduced but not inhibited by CRF-R1 blockade. We hypothesize that CRF action within the central nervous system can regulate the hyperglycemic response to surgical stress via mechanisms other than the pituitary-adrenal axis. Our results also indicate that the hypothalamic stress response after surgical stress is dependent on other factors apart from CRF.

Topics: Acute Disease; Adrenocorticotropic Hormone; Animals; Biological Transport; Blood Glucose; Corticosterone; Dexamethasone; Glucocorticoids; Glucose; Hyperglycemia; Insulin; Male; Muscle, Skeletal; Phosphatidylinositol 3-Kinases; Pyrimidines; Pyrroles; Rats; Rats, Wistar; Receptors, Corticotropin-Releasing Hormone; Wounds and Injuries