Microinjection of kappa opioid receptor (KOR) agonists into the rostral ventromedial medulla (RVM) attenuates mu-opioid receptor mediated antinociception and stress-induced analgesia, yet is also reported to have an analgesic effect. To determine how KOR agonists produce both antinociceptive and antianalgesic actions within the RVM, the KOR agonist U69593 was microinjected directly into the RVM...

Salvinorin A, a neoclerodane diterpene, is the most potent naturally occurring hallucinogen known and rivals the synthetic hallucinogen lysergic acid diethylamide in potency. Recently, the molecular target of salvinorin A was identified as the kappa opioid receptor (KOR). Salvinorin A represents the only known non-nitrogenous KOR selective agonist. Based on the selectivity of salvinorin A for t...

The ability of neuropeptide Y to potently stimulate food intake is dependent in part upon the functioning of mu and kappa opioid receptors. The combined use of selective opioid antagonists directed against mu, delta or kappa receptors and antisense probes directed against specific exons of the MOR-1, DOR-1, KOR-1 and KOR-3/ORL-1 opioid receptor genes has been successful in characterizing the pr...

There is considerable interest in understanding the regulation of peripheral opioid receptors to avoid central nervous system side effects associated with systemically administered opioid analgesics. Here, we investigated the regulation of the κ-opioid receptor (KOR) on rat primary sensory neurons in vitro and in a rat model of thermal allodynia. Under basal conditions, application of the KOR a...

Background: Prescription opioid addiction is a significant health problem characterized by compulsive drug seeking, withdrawal and chronic relapse. We investigated the neurobiological consequences of escalation of prescription opioid use using extended access to intravenous oxycodone self-administration in rats. Methods: Male Wistar rats acquired oxycodone self-administration (0.15 mg/kg/infusi...

This study examined adaptive changes in protein kinase A (PKA) and kappa opioid receptor (KOR) in selected addiction-related brain regions before and after conditioned place aversion (CPA). Seventy-two male SD rats were randomly assigned to an experimental group (morphine + naloxone, "MN") and 2 control groups: MS (morphine + saline) and SN (saline + naloxone). MN rats were intraperitoneally in...

Microinjection of kappa opioid receptor (KOR) agonists into the rostral ventromedial medulla (RVM) attenuates mu-opioid receptor mediated antinociception and stress-induced analgesia, yet is also reported to have an analgesic effect. To determine how KOR agonists produce both antinociceptive and anti-analgesic actions within the RVM, the KOR agonist U69593 was microinjected directly into the RV...

This study combines functional and anatomical characterization of neurons in the rostral ventromedial medulla (RVM) to show distinct neurochemical phenotypes between functional classes of neurons. The RVM contains three functional classes of neurons: off cells show a pause in spontaneous activity prior to a nociceptive withdrawal reflex; on cell activity increases prior to a nociceptive reflex;...

The corticotropin-releasing factor (CRF) and kappa-opioid receptor (KOR) systems are both implicated in stress-related behaviors and drug dependence. Although previous studies suggest that antagonism of each system blocks aspects of experimental models of drug dependence, the possible interaction between these systems at the neuronal level has not been completely examined. We used an in vitro b...

The authors review the opioid literature for evidence of increased analgesia and reduced adverse side effects by combining mu-opioid-receptor (MOR) agonists, kappa-opioid-receptor (KOR) agonists, and nonselective low-dose-opioid antagonists (LD-Ant). We tested fentanyl (MOR agonist) and spiradoline (KOR agonist), singly and combined, against somatic and visceral pain models. Combined agonists i...