naltrindole and Anxiety-Disorders

We previously reported that systemic administration of a selective delta opioid receptor (DOP) agonist, KNT-127, produced potent anxiolytic-like effects in rats. Interestingly, DOPs are highly distributed in the basolateral region of the amygdala (BLA).. In this study, we investigated the effect of intra-BLA administration of KNT-127 on anxiety-like behaviors in rats.. In the elevated plus maze test, bilateral injection of KNT-127 into the BLA significantly and dose-dependently increased time spent in the open arms. The magnitude of KNT-127 (0.08 μg/0.2 μl)-induced anxiolytic-like effects was similar to muscimol (0.1 μg/0.2 μl), which is a selective agonist for the gamma amino butyric acid type A receptors. Further, anxiolytic-like effects of KNT-127 were abolished by pretreatment with naltrindole, a selective DOP antagonist, suggesting that KNT-127-induced anxiolytic-like effects are mediated by DOPs. These anxiolytic-like effects were confirmed using another innate anxiety model, the open field test. Interestingly, intra-BLA administration of KNT-127 also induced anxiolytic-like effects in the contextual fear conditioning test. Moreover, these effects were also abolished by naltrindole pretreatment. Finally, we demonstrated that intra-BLA administration of KNT-127 facilitates extinction learning of contextual fear in conditioned rats.. Altogether, our findings clearly demonstrate that intra-BLA administration of KNT-127 in rats has robust anxiolytic-like effects not only in innate anxiety-like behavioral tests but also in the contextual fear conditioning test.

Topics: Amygdala; Animals; Anti-Anxiety Agents; Anxiety; Anxiety Disorders; Basolateral Nuclear Complex; Fear; Learning; Male; Morphinans; Muscimol; Naltrexone; Rats; Rats, Wistar; Receptors, Opioid, delta

It has been widely recognized that chronic pain could cause physiological changes at supraspinal levels. The delta-opioidergic system is involved in antinociception, emotionality, immune response and neuron-glia communication. In this study, we show that mice with chronic pain exhibit anxiety-like behavior and an increase of astrocytes in the cingulate cortex due to the dysfunction of cortical delta-opioid receptor systems. Using neural stem cells cultured from the mouse embryonic forebrain, astrocyte differentiation was clearly observed following long-term exposure to the selective delta-opioid receptor antagonist, naltrindole. We also found that micro-injection of either activated astrocyte or astrocyte-conditioned medium into the cingulate cortex of mice aggravated the expression of anxiety-like behavior. Our results indicate that the chronic pain process promotes astrogliosis in the cingulate cortex through the dysfunction of cortical delta-opioid receptors. This phenomenon may lead to emotional disorders including aggravated anxiety under chronic pain-like state.

Topics: Animals; Anxiety Disorders; Astrocytes; Brain Tissue Transplantation; Cells, Cultured; Cerebral Cortex; Chronic Disease; Culture Media, Conditioned; Disease Models, Animal; Gliosis; Gyrus Cinguli; Male; Mice; Mice, Inbred C57BL; Naltrexone; Narcotic Antagonists; Neuralgia; Pain, Intractable; Peripheral Nervous System Diseases; Receptors, Opioid, delta; Sciatic Neuropathy; Stem Cells

Recent studies have revealed the participation of the endogenous opioid system in several behavioural responses induced by nicotine including antinociception, rewarding properties, and physical drug dependence.. The present study was designed to examine the possible involvement of the various opioid receptors in the anxiolytic- and anxiogenic-like responses induced by nicotine in mice.. The acute administration of low (0.05) or high (0.8 mg/kg) doses of nicotine subcutaneously produced opposite effects in the elevated plus maze, i.e. anxiolytic- and anxiogenic-like responses, respectively. Animals were only exposed once to nicotine. The effects of the pretreatment with the mu-opioid receptor antagonist, beta-funaltrexamine (5 mg/kg), the delta-opioid antagonist, naltrindole (2.5 mg/kg) and the kappa-opioid antagonist, nor-binaltorphimine (2.5 mg/kg) intraperitoneally were evaluated on the anxiolytic- and anxiogenic-like responses induced by nicotine.. beta-funaltrexamine, but not nor-binaltorphimine or naltrindole, abolished nicotine-induced anxiolytic-like effects, suggesting an involvement of mu-opioid receptors in this behavioural response. On the other hand, naltrindole, but not nor-binaltorphimine or beta-funaltrexamine, increased the anxiogenic-like responses of nicotine, suggesting an involvement of delta-receptors in this behavioural effect.. These results demonstrate that the endogenous opioid system is involved in the effects induced by nicotine on anxiety-like behaviour and provide new findings to further clarify the interaction between these two neurochemical systems.

Topics: Analysis of Variance; Animals; Anxiety Disorders; Behavior, Animal; Dose-Response Relationship, Drug; Drug Antagonism; Drug Synergism; Injections, Intraperitoneal; Injections, Subcutaneous; Male; Maze Learning; Mecamylamine; Mice; Naltrexone; Narcotic Antagonists; Nicotine; Nicotinic Agonists; Nicotinic Antagonists; Receptors, Opioid