Acute withdrawal from chronic escalating-dose binge cocaine administration alters kappa opioid receptor stimulation of [35S] guanosine 5′-O-[gamma-thio]triphosphate acid binding in the rat ventral tegmental area

Although kappa- and delta-opioid receptors on mammalian cardiac myocytes have been discovered recently, the intracellular effects that result from stimulation of these receptors remain unknown. We examine the effects of a rapid and brief exposure to a kappa-opioid receptor agonist on intracellular Ca2+, pH, and cell length in individual isolated rat ventricular cells. The specific kappa-agonist trans-dl-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]- benzene-acetamide (U-50488H) (methane sulfonate salt) caused a transient increase in cytosolic pH (pHi) measured from the change in SNARF-1 fluorescence and an increase in cytosolic [Ca2+] (Cai), indexed by a change in indo-1 fluorescence. The initial Cai increase often was followed by Cai oscillations. Both pHi and Cai effects were blocked by the specific antagonist kappa-opioid receptor l-(N-furylmethyl)-alpha-normetazocine methane-sulfonate (Mr 1452). The amplitude of contraction that accompanied the Cai increase elicited by U-50488H was greater than that associated with a similar increase in Cai elicited by electrical stimulation or by the rapid exposure of cells to caffeine. Thus an acute and brief kappa-opioid receptor stimulation of cardiac cells leads to an increase in Cai and pHi. The pHi increase was abolished by 1) blockade of the Na(+)-H+ exchanger by ethyl isopropyl amiloride and 2) inhibition of protein kinase C (PKC) activity via pretreatment with staurosporine or prolonged incubation with 4 beta-phorbol 12-myristate 13-acetate. These maneuvers did not abolish the U-50488H-induced increase in Ca.(ABSTRACT TRUNCATED AT 250 WORDS)

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Developmental changes in the behavioral and autonomic effects of kappa opioid receptor stimulation of the midbrain periaqueductal gray

Developmental Psychobiology ◽

10.1002/dev.20039 ◽

2004 ◽

Vol 46 (1) ◽

pp. 47-56 ◽

Cited By ~ 7

Author(s):

Gregory A. Goodwin ◽

Gordon A. Barr

Keyword(s):

Opioid Receptor ◽

Periaqueductal Gray ◽

Kappa Opioid Receptor ◽

Developmental Changes ◽

Kappa Opioid ◽

Receptor Stimulation ◽

Stimulation Of

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A midbrain dynorphin circuit promotes threat generalization

10.1101/2020.04.21.053892 ◽

2020 ◽

Cited By ~ 1

Author(s):

Lizz Fellinger ◽

Yong S. Jo ◽

Avery C. Hunker ◽

Marta E. Soden ◽

Larry S. Zweifel

Keyword(s):

Ventral Tegmental Area ◽

Opioid Receptor ◽

Dorsal Raphe Nucleus ◽

Kappa Opioid Receptor ◽

Raphe Nucleus ◽

Stria Terminalis ◽

Kappa Opioid ◽

Bed Nucleus ◽

Ventral Tegmental ◽

Threat Stimuli

SummaryDiscrimination between predictive and non-predictive threat stimuli decrease as threat intensity increases. The central mechanisms that mediate the transition from discriminatory to generalized threat responding remain poorly resolved. Here, we identify the stress- and dysphoria-associated kappa opioid receptor (KOR) and its ligand dynorphin (Dyn), acting in the ventral tegmental area (VTA), as a key substrate for regulating threat generalization. We identified several dynorphinergic inputs to the VTA and demonstrate that projections from the bed nucleus of the stria terminalis (BNST) and dorsal raphe nucleus (DRN) both contribute to anxiety-like behavior but differentially affect threat generalization. These data demonstrate that conditioned threat discrimination has an inverted ‘U’ relationship with threat intensity and establish a role for KOR/Dyn signaling in the midbrain for promoting threat generalization.

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Behavioral effects of kappa-opioid-receptor stimulation on neonatal rats.

Behavioral Neuroscience ◽

10.1037/0735-7044.108.2.418 ◽

1994 ◽

Vol 108 (2) ◽

pp. 418-423 ◽

Cited By ~ 30

Author(s):

Priscilla Kehoe ◽

Carolyn B. Boylan

Keyword(s):

Opioid Receptor ◽

Kappa Opioid Receptor ◽

Behavioral Effects ◽

Neonatal Rats ◽

Kappa Opioid ◽

Receptor Stimulation

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The KCa channel as a trigger for the cardioprotection induced by kappa-opioid receptor stimulation - its relationship with protein kinase C

British Journal of Pharmacology ◽

10.1038/sj.bjp.0706268 ◽

2005 ◽

Vol 145 (7) ◽

pp. 984-991 ◽

Cited By ~ 27

Author(s):

Chun-Mei Cao ◽

Mai Chen ◽

Tak-Ming Wong

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Opioid Receptor ◽

Kappa Opioid Receptor ◽

Kappa Opioid ◽

Receptor Stimulation ◽

Kinase C

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Activation of the kappa opioid receptor / dynorphin system alters stress and threat responding during acute withdrawal from intermittent alcohol drinking in male mice

10.1101/2020.09.23.310284 ◽

2020 ◽

Author(s):

Lara S. Hwa ◽

Sofia Neira ◽

Dipanwita Pati ◽

Melanie M. Pina ◽

Morgan Bowling ◽

...

Keyword(s):

Opioid Receptor ◽

Alcohol Drinking ◽

Kappa Opioid Receptor ◽

Predator Odor ◽

List Type ◽

Kappa Opioid ◽

Swim Stress ◽

Acute Withdrawal ◽

Stress Behavior ◽

Forced Swim

AbstractThe dynorphin/kappa opioid receptor (KOR) system in the brain regulates both stressful experiences and negative, aversive states during withdrawal from drugs of abuse. We explored the role of this system during acute withdrawal from long-term alcohol drinking, focusing on the bed nucleus of the stria terminalis (BNST), a region strongly implicated in alcohol-withdrawal induced alterations of behavior. Male C57BL/6J mice were subjected to repeated forced swim tests, home cage exposure to a predator odor, and a visual threat after eight weeks intermittent access to alcohol or water. Systemic injection of KOR antagonist norBNI reversed alcohol-related differences in immobility time during the second swim test and reduced burying behavior in response to predator odor, but did not affect behavioral response to visual threat. In dynorphin-GFP reporter mice, c-Fos immunoreactivity was increased in dynorphin-containing neurons after repeated swim stress and alcohol drinking. Using dynorphin-GFP mice, there was enhanced spontaneous excitatory synaptic drive onto dynorphin neurons in the BNST after alcohol-drinking mice underwent forced swim stress. Finally, knockdown of dynorphin in the BNST using a viral shRNA affected swim stress behavior and responses to TMT in alcohol drinkers and controls, but did not affect alcohol drinking. These studies confirm BNST dynorphin recruitment during acute withdrawal as playing a key role in altered behavioral responses to stressful stimuli.HighlightsIntermittent alcohol drinking changed stress reactions in mice.KOR antagonist norBNI altered stress responses in alcohol drinkers.Alcohol and swim stress increased c-Fos immunoreactivity in BNST dynorphin neurons.Swim stress enhanced excitatory drive onto BNST dynorphin cells in alcohol mice.BNST dynorphin knockdown affected some stress behavior, but not alcohol drinking.

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