Coordinate regulation of noradrenergic and serotonergic brain regions by amygdalar neurons

Based on the importance of the locus coeruleus-norepinephrine (LC-NE) system and the dorsal raphe nucleus-serotonergic (DRN-5-HT) system in stress-related pathologies, additional understanding of brain regions coordinating their activity is of particular interest. One such candidate is the amygdalar complex, and specifically, the central nucleus (CeA), which has been implicated in emotional arousal and is known to send monosynaptic afferent projections to both these regions. Our present data using dual retrograde tract tracing is the first to demonstrate a population of amygdalar neurons that project in a collateralized manner to the LC and DRN, indicating that amygdalar neurons are positioned to coordinately regulate the LC and DRN, and links these brain regions by virtue of a common set of afferents. Further, we have also characterized the phenotype of a population of these collaterally projecting neurons from the amygdala as containing corticotropin releasing factor or dynorphin, two peptides heavily implicated in the stress response. Understanding the co-regulatory influences of this limbic region on 5HT and NE regions may help fill a gap in our knowledge regarding neural circuits impacting these systems and their adaptations in stress.     

Determination of specific neuropeptides modulation time course in a rat model of osteoarthritis pain by liquid chromatography ion trap mass spectrometry

Animal models are useful to evaluate pharmacological therapies to alleviate joint pain. The present study characterized central neuropeptides modulation in the monoiodoacetate (MIA) rat model. Animals receiving a single 3 mg MIA injection were euthanized at 3, 7, 14, 21 and 28 days post injection. Spinal cords were analyzed by liquid chromatography ion trap mass spectrometry. Up-regulations of the calcitonin gene-related peptide and substance P were observed starting on days 7 and 28 respectively, whereas big dynorphin_(1–32) content decreased significantly on day 14 in comparison to control animals (P < 0.05). Preclinical drug evaluations using this model should be conducted between 7 and 21 days post injection when the lesions resemble most to human osteoarthritis.     

Blockade of ethanol reward by the kappa opioid receptor agonist U50,488H

Alcoholism is a pervasive social problem, and thus understanding factors that regulate alcohol (ethanol) reward is important for designing effective therapies. One putative regulatory system includes the kappa opioid receptor (KOR) and its endogenous ligand, dynorphin. Previously, we demonstrated that acute ethanol increased preprodynorphin expression via brain-derived neurotrophic factor (BDNF) in striatal neurons, and that blockade of the KOR attenuated decreases in ethanol intake observed following increased expression of BDNF. As high doses of KOR agonists can generate an aversive state, we hypothesized that endogenous dynorphin may regulate ethanol intake by interfering with the rewarding properties of ethanol. We found that low, nonaversive doses of the KOR agonist U50,488H blocked the rewarding properties of ethanol during conditioning, thus impairing the acquisition of conditioned place preference. Importantly, we demonstrate that U50,488H also inhibited the conditioned increase in locomotor activation normally observed in the ethanol-paired chamber on test day. Taken together, these data indicate that the KOR/dynorphin system may acutely regulate ethanol intake via inhibition of the rewarding properties of ethanol.     

慢性乙醇中毒大鼠脑内内源性阿片肽系统含量的改变

目的观察慢性乙醇中毒大鼠下丘脑、纹状体以及海马内源性阿片肽,即β-内啡肽（β-endorphine,β—EP）、甲硫脑啡肽（met—enkephalin,MENK）、亮脑啡肽（1eu—enkephalin,LENK）和强啡肽A（dynorphin A,Dyn A）含量的变化,并记录其血中乙醇浓度的变化,以探讨乙醇对中神经系统的损害与内源性阿片肽系统的关系。方法用成年Wistar大鼠建立慢性乙醇中毒大鼠动物模型。结果慢性乙醇中毒后大鼠下丘脑、纹状体以及海马内β-EP,LENK以及DynA含量均有不同程度的降低（P〈0．05或P〈0．01）,MENK在下丘脑和海马含量变化不大（P〉0．05）,只有纹状体内MENK的含量降低（P〈0．05）。结论慢性乙醇中毒时下丘脑、纹状体以及海马内源性阿片肽含量有不同程度的下降,这可能与乙醇奖赏效应的发生以及学习记忆障碍有关。     

急性乙醇中毒大鼠下丘脑阿片肽含量的变化及葛根素的干预研究

目的观察急性乙醇中毒大鼠下丘脑β-内啡肽（β—endorphine,β—EP）、亮脑啡肽（leu—enkephalin,LENK）和强啡肽A（dynorphin A,DynA）含量变化及葛根素的干预作用。方法选雄性Wistar大鼠30只,随机分为对照组、模型组和葛根素组,分别测定血中乙醇浓度变化,下丘脑β—EP,LENK,Dyn A的含量。结果葛根素组的血乙醇浓度比模型组低,与对照组相比,模型组大鼠下丘脑β-EP,LENK水平显著增高,DynA的含量变化不明显。葛根素组与模型组相比,β-EP,LENK水平均显著降低,Dyn A含量变化不明显。结论急性乙醇中毒时阿片肽释放增加,葛根素可能通过降低血乙醇浓度来抑制阿片肽的释放,对乙醇中毒起到治疗作用。