Abstract
Anxiety disorders affect roughly 40 million American adults in a given year. Those suffering from anxiety disorders often experience additional stress-linked illnesses, such as depression. Previous research has shown that stress exposure increases levels of the endogenous neuropeptide dynorphin, which the kappa opioid system is selectively activated by. This study examined the role of the kappa opioid system in regulating stress-related behavior using the elevated plusmaze. Behavioral stress responses were examined in male Wistar rats following i.p. administration of opioid agonist U-50,488 (0 or 10 mg/kg). Subjects were pretreated with the kappa opioid antagonist nor-binaltorphimine (nor-BNI) 24 hours prior to testing in the elevated plus-maze (0 or 20 mg/kg). Injections of 10 mg/kg U-50,488 significantly decreased percent open arm time compared to controls, an effect reversed by pretreatment with 20 mg/kg nor-BNI (F(1,44) = 6.10, p< 0.05). A main effect of nor-BNI was found on the total number of arm entries (F(1,44) = 11.73, p < 0.05). Further analysis revealed that pretreatment with nor-BNI led to an increased number of arm entries in rats injected with U-50,488. The nor-BNI sensitivity of the behavioral responses suggests an activation of the kappa opioid receptors by a stress-induced release of dynorphin. The results indicate a relationship between kappa opioid receptors and stress-related behaviors and illustrate the potential therapeutic value of targeting the kappa opioid system in the treatment of anxiety and other stress-related disorders. Introduction