Blockade of dorsal hippocampal kappa-opioid receptors increases blood pressure in normotensive and isolation-induced hypertensive rats

Wright, Rebecca C; Ingenito, Alphonse J.

doi:10.1016/s0143-4179(03)00024-6

Cited by 10 publications

(7 citation statements)

References 12 publications

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“…Similar to spontaneous locomotor activity, social isolation in the cages during hindlimb unloading caused notable changes in cardiovascular parameters, with the most significant increase occurring in blood pressure during daylight. Social isolation in individual cages causes behavioral changes in rats and can be used as a model for psychosocial-stress, which induces reversible hypertension accompanied by cardiovascular structural changes, such as left ventricular and aorta hypertrophy [35]–[39]. An increase in blood pressure can be reversed by treatment with β-adrenoreceptor antagonists, and is preventable by pretreatment [35].…”

Section: Discussionmentioning

confidence: 99%

Contribution of Social Isolation, Restraint, and Hindlimb Unloading to Changes in Hemodynamic Parameters and Motion Activity in Rats

et al. 2012

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The most accepted animal model for simulation of the physiological and morphological consequences of microgravity on the cardiovascular system is one of head-down hindlimb unloading. Experimental conditions surrounding this model include not only head-down tilting of rats, but also social and restraint stresses that have their own influences on cardiovascular system function. Here, we studied levels of spontaneous locomotor activity, blood pressure, and heart rate during 14 days under the following experimental conditions: cage control, social isolation in standard rat housing, social isolation in special cages for hindlimb unloading, horizontal attachment (restraint), and head-down hindlimb unloading. General activity and hemodynamic parameters were continuously monitored in conscious rats by telemetry. Heart rate and blood pressure were both evaluated during treadmill running to reveal cardiovascular deconditioning development as a result of unloading. The main findings of our work are that: social isolation and restraint induced persistent physical inactivity, while unloading in rats resulted in initial inactivity followed by normalization and increased locomotion after one week. Moreover, 14 days of hindlimb unloading showed significant elevation of blood pressure and slight elevation of heart rate. Hemodynamic changes in isolated and restrained rats largely reproduced the trends observed during unloading. Finally, we detected no augmentation of tachycardia during moderate exercise in rats after 14 days of unloading. Thus, we concluded that both social isolation and restraint, as an integral part of the model conditions, contribute essentially to cardiovascular reactions during head-down hindlimb unloading, compared to the little changes in the hydrostatic gradient.

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Section: Discussionmentioning

confidence: 99%

Contribution of Social Isolation, Restraint, and Hindlimb Unloading to Changes in Hemodynamic Parameters and Motion Activity in Rats

et al. 2012

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“…Notably, ligand autoradiography studies (144, 193, 226, 227, 229, 230, 343, 346) failed to detect significant kappa binding in the hippocampus, although consistent pharmacological and electrophysiological data indicate the presence of kappa receptors in this region (for example, Refs. 89, 106, 207, 340, 416). …”

Section: Anatomy Of the Brain Opioid Systemmentioning

confidence: 99%

Reward Processing by the Opioid System in the Brain

Merrer¹,

Becker²,

Befort³

et al. 2009

Physiological Reviews

852

676

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The opioid system consists of three receptors, mu, delta, and kappa, which are activated by endogenous opioid peptides processed from three protein precursors, proopiomelanocortin, proenkephalin, and prodynorphin. Opioid receptors are recruited in response to natural rewarding stimuli and drugs of abuse, and both endogenous opioids and their receptors are modified as addiction develops. Mechanisms whereby aberrant activation and modifications of the opioid system contribute to drug craving and relapse remain to be clarified. This review summarizes our present knowledge on brain sites where the endogenous opioid system controls hedonic responses and is modified in response to drugs of abuse in the rodent brain. We review 1) the latest data on the anatomy of the opioid system, 2) the consequences of local intracerebral pharmacological manipulation of the opioid system on reinforced behaviors, 3) the consequences of gene knockout on reinforced behaviors and drug dependence, and 4) the consequences of chronic exposure to drugs of abuse on expression levels of opioid system genes. Future studies will establish key molecular actors of the system and neural sites where opioid peptides and receptors contribute to the onset of addictive disorders. Combined with data from human and nonhuman primate (not reviewed here), research in this extremely active field has implications both for our understanding of the biology of addiction and for therapeutic interventions to treat the disorder.

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“…While KOR antagonists have been at the forefront of treatment options for psychiatric illnesses, they are also implicated in a medley of other physiological disorders, including salt consumption (Nascimento et al 2012), epilepsy and hypertension (though hypertension is not discussed here, see(Wright & Ingenito 2001, Wright & Ingenito 2003, Wright et al 2000) for further reading). This brings together the importance of the “whole body” perspective when considering KOR drugs as therapeutic treatment for brain-related diseases.…”

Section: Conclusion: Role Of Kors In Stress and Anxiety Potential Asmentioning

confidence: 99%

Kappa opioid receptor signaling in the brain: Circuitry and implications for treatment

Crowley

Kash

2015

Progress in Neuro-Psychopharmacology and Biological Psychiatry

106

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Kappa opioid receptors (KORs) in the central nervous system have been known to be important regulators of a variety of psychiatry illnesses, including anxiety and addiction, but their precise involvement in these behaviors is complex and has yet to be fully elucidated. Here, we briefly review the pharmacology of KORs in the brain, including KOR's involvement in anxiety, depression, and alcohol addiction. We also review the known neuronal circuitry impacted by KOR signaling, and interactions with corticotrophin-releasing factor (CRF), another key peptide in anxiety-related illnesses, as well as the role of glucocorticoids. We suggest that KORs are a promising therapeutic target for a host of neuropsychiatric conditions.

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Blockade of dorsal hippocampal kappa-opioid receptors increases blood pressure in normotensive and isolation-induced hypertensive rats

Cited by 10 publications

References 12 publications

Contribution of Social Isolation, Restraint, and Hindlimb Unloading to Changes in Hemodynamic Parameters and Motion Activity in Rats

Contribution of Social Isolation, Restraint, and Hindlimb Unloading to Changes in Hemodynamic Parameters and Motion Activity in Rats

Reward Processing by the Opioid System in the Brain

Kappa opioid receptor signaling in the brain: Circuitry and implications for treatment

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