Kappa opioid agonists produce anxiolytic-like behavior on the elevated plus-maze

Privette, T.H.; Terrian, David M.

doi:10.1007/bf02245945

Cited by 74 publications

(48 citation statements)

References 44 publications

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“…However, inconsistent with these observations is the finding that the κ opioid receptor agonist U50488 significantly increased time spent in open arms during the EPM test [42,43] . This is consistent with work demonstrating that U69593 and salvinorin A both produced anxiolytic effects in rodents [44,45] . Microinjection of U69593 into the infralimbic cortex reduced anxiety-like behavior in the EPM test [46] .…”

Section: Rodent Models Of Anxietysupporting

confidence: 91%

“…Discrepancies among these studies may be due to, but are not limited to, the use of specific genetic constructs for generating mutant mice, experimental paradigms, size of the apparatus, intensity of illumination, test conditions, animal strains, and lab specific basal stress levels. Although with these limitations and variables, the findings clearly demonstrate that the dynorphin/κ opioid receptor system is involved in anxiety-related behavior [33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][49][50][51] (see Table 1 for a summary of current literature), but it is difficult to define the exact role of κ opioid receptor signaling because both anxiolyticand anxiogenic-like effects are reported with κ opioid receptor agonists. Indeed, THC, a CB1 receptor agonist, microinjected at low doses in the prefrontal cortex and ventral hippocampus induced an anxiolytic-like response, while high doses caused an anxiogenic reaction [52] .…”

Section: Rodent Models Of Anxietymentioning

confidence: 99%

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The role of the dynorphin/κ opioid receptor system in anxiety

Hang

Wang

et al. 2015

Acta Pharmacol Sin

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Anxiety disorders are the most common and prevalent forms of psychiatric disease, although the biological basis of anxiety is not well understood. The dynorphin/κ opioid receptor system is widely distributed in the central nervous system and has been shown to play a critical role in modulating mood and emotional behaviors. In the present review, we summarize current literature relating to the role played by the dynorphin/κ opioid receptor system in anxiety and κ opioid receptor antagonists as potential therapeutic agents for the treatment of anxiety disorders.

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Section: Rodent Models Of Anxietysupporting

confidence: 91%

Section: Rodent Models Of Anxietymentioning

confidence: 99%

The role of the dynorphin/κ opioid receptor system in anxiety

Hang

Wang

et al. 2015

Acta Pharmacol Sin

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“…Selective k-opioid agonists have been found to exhibit anxiolytic properties in rodents (Privette and Terrian, 1995). Moreover, the anticonflict effect of diazepam was abolished by pretreatment with naloxone or nor-BNI suggesting that endogenous dynorphins play a role in the regulation of anxiety (Tsuda et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Big Dynorphin, a Prodynorphin-Derived Peptide Produces NMDA Receptor-Mediated Effects on Memory, Anxiolytic-Like and Locomotor Behavior in Mice

Kuzmin

Madjid

Terenius

et al. 2005

Neuropsychopharmacol

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Effects of big dynorphin (Big Dyn), a prodynorphin-derived peptide consisting of dynorphin A (Dyn A) and dynorphin B (Dyn B) on memory function, anxiety, and locomotor activity were studied in mice and compared to those of Dyn A and Dyn B. All peptides administered i.c.v. increased step-through latency in the passive avoidance test with the maximum effective doses of 2.5, 0.005, and 0.7 nmol/animal, respectively. Effects of Big Dyn were inhibited by MK 801 (0.1 mg/kg), an NMDA ion-channel blocker whereas those of dynorphins A and B were blocked by the k-opioid antagonist nor-binaltorphimine (6 mg/kg). Big Dyn (2.5 nmol) enhanced locomotor activity in the open field test and induced anxiolytic-like behavior both effects blocked by MK 801. No changes in locomotor activity and no signs of anxiolytic-like behavior were produced by dynorphins A and B. Big Dyn (2.5 nmol) increased time spent in the open branches of the elevated plus maze apparatus with no changes in general locomotion. Whereas dynorphins A and B (i.c.v., 0.05 and 7 nmol/animal, respectively) produced analgesia in the hot-plate test Big Dyn did not. Thus, Big Dyn differs from its fragments dynorphins A and B in its unique pattern of memory enhancing, locomotor-and anxiolytic-like effects that are sensitive to the NMDA receptor blockade. The findings suggest that Big Dyn has its own function in the brain different from those of the prodynorphin-derived peptides acting through k-opioid receptors.

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“…Preproenkephalin knockout mice have elevated level of anxiety-like behavior and aggression (Konig et al 1996), and some novel -opioid agonists show anxiolytic properties (Privette and Terrian 1995). Several lines of evidence also indicate the involvement of endogenous opioid peptides in various aspects of benzodiazepine action, including their influences on food intake, locomotor activity, conflict, and anxiety-like behaviors (Millan and Duka 1981;Cooper 1983;Nowakowska and Chodera 1990).…”

mentioning

confidence: 99%

Overexpression of Proenkephalin in the Amygdala Potentiates the Anxiolytic Effects of Benzodiazepines

Wen

Wilson

2000

Neuropsychopharmacology

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To elucidate the role of opioid peptides in control of the anxiety-like behavior and anxiety-reducing actions of benzodiazepines, a recombinant, replication-defective herpes virus (SHPE) carrying human preproenkephalin cDNA was delivered to rat amygdala. Viral infection resulted in a strong, localized transgene expression after 2-4 days which diminished after one week. Anxiety-like behavior and the anxiolytic effect of diazepam were assessed three days afterIn addition to its well known role in mediating fear and anxiety responses (Davis et al. 1994), the amygdala may also be a key neural substrate for the anxiolytic actions of benzodiazepines. Benzodiazepines (BZs) are believed to induce their anxiolytic properties by binding to GABA/benzodiazepine receptors in the brain (Haefely 1990). In addition, the amygdala has a high density of GABA/benzodiazepine receptors (Young and Kuhar 1980;Richards and Mohler 1984). Local infusion of benzodiazepine agonists into the amygdala produces anxiolytic effects which can be blocked by co-administration of GABA A or benzodiazepine antagonists (Scheel-Kruger and Petersen 1982;Petersen et al. 1985; Treit 1994, 1995). Furthermore, the anxietyreducing actions of systemic benzodiazepines can be blocked by intra-amygdala injection of GABA/benzodiazepine antagonists (Sanders and Shekhar 1995).The amygdala also has high levels of endogenous opioid peptides and opioid receptors (Loughlin et al. 1995), and opioid mechanisms have been implicated in many biological functions, including nociception, memory, and fear conditioning (Good and Westbrook 1995;McGaugh et al. 1996;Valverde et al. 1996). A partial anxiolytic action has been reported following microinjection of morphine into amygdala (File and Rodgers 1979).Although opioid agonists are not used as anxiolytics in general, recent evidence strongly indicates a role for endogenous opioid peptides in the control of stress and anxiety (Olson et al. 1996). Preproenkephalin knockout (Konig et al. 1996), and some novel -opioid agonists show anxiolytic properties (Privette and Terrian 1995). Several lines of evidence also indicate the involvement of endogenous opioid peptides in various aspects of benzodiazepine action, including their influences on food intake, locomotor activity, conflict, and anxiety-like behaviors (Millan and Duka 1981;Cooper 1983;Nowakowska and Chodera 1990). Interestingly, clinical studies suggest interactions between responses to benzodiazepines and opioids in humans (Darke et al. 1993). The anxiolytic effects of benzodiazepines can be blocked by opioid antagonists in both humans and laboratory animals (Billingsley and Kubena 1978;Koob et al. 1980;Duka et al. 1981Duka et al. , 1982Agmo et al 1995;Tsuda et al. 1996).Prior studies using herpes virus-mediated gene transfer demonstrated that overexpression of proenkephalin in amygdala produced antinociceptive effects, and illustrated the usefulness of this methodology for examining the role of neuropeptides in behavioral responses (Kang et al. 1998). To investigate if mo...

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Kappa opioid agonists produce anxiolytic-like behavior on the elevated plus-maze

Cited by 74 publications

References 44 publications

The role of the dynorphin/κ opioid receptor system in anxiety

The role of the dynorphin/κ opioid receptor system in anxiety

Big Dynorphin, a Prodynorphin-Derived Peptide Produces NMDA Receptor-Mediated Effects on Memory, Anxiolytic-Like and Locomotor Behavior in Mice

Overexpression of Proenkephalin in the Amygdala Potentiates the Anxiolytic Effects of Benzodiazepines

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