Involvement of δ-opioid receptors in the effects induced by endogenous enkephalins on learned helplessness model

Tejedor-Real, P.; Micó, Juan Antonio; Smadja, Claire; Maldonado, Rafaël; Roques, Bernárd P.; Gibert-Rahola, J.

doi:10.1016/s0014-2999(98)00423-3

Cited by 95 publications

(50 citation statements)

References 51 publications

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“…Moreover, delta receptor agonists and enkephalinase inhibitors modify the escape behavior in the learned helplessness model although at high doses they are also epileptogenic (Tejedor-Real et al, 1998). Under basal conditions, enkephalin mRNA expression in dentate gyrus is higher in the FRL than in the FSL rats.…”

Section: Antidepressant-like Effect Of Running In Fsl Rats Is Not Depmentioning

confidence: 98%

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Running has Differential Effects on NPY, Opiates, and Cell Proliferation in an Animal Model of Depression and Controls

Bjørnebekk

Mathé

Brené

2005

Neuropsychopharmacol

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Physical activity has documented beneficial effect in treatment of depression. Recently, we found an antidepressant-like effect of running in an animal model of depression, the Flinders Sensitive Line (FSL) and demonstrated that it was associated with increased hippocampal cell proliferation. In this study, we analyzed levels of mRNAs encoding the neuropeptide Y (NPY) and the opioid peptides dynorphin and enkephalin in hippocampus and correlated these to cell proliferation in the FSL and in the 'nondepressed' Flinders Resistant Line (FRL) strain, with/without access to running wheels. Running increased NPY mRNA in dentate gyrus and the CA4 region in FSL, but not in FRL rats. NPY mRNA increase was correlated to increased cell proliferation in the subgranular zone of dentate gyrus. Baseline dynorphin and enkephalin mRNA levels in the dentate gyrus were lower in the FSL compared to the FRL strain. Running had no effect on dynorphin and enkephalin mRNAs in the FSL strain but it decreased dynorphin mRNA, and there was a trend to increased enkephalin mRNA in the FRL rats. Thus, it would appear that the CNS effects of running are different in 'depressed' and control animals; modification of NPY, a peptide associated with depression and anxiety, in depressed animals, vs effects on opioids, associated with the reward systems, in healthy controls. Our data support the hypothesis that NPY neurotransmission in hippocampus is malfunctioning in depression and that antidepressive treatment, in this case wheel running, will normalize it. In addition, we also show that the increased NPY after running is correlated to increased cell proliferation, which is associated with an antidepressive-like effect.

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Section: Antidepressant-like Effect Of Running In Fsl Rats Is Not Depmentioning

confidence: 98%

“…Thus, mice with a deletion of delta receptors have increased anxiety and 'depression'. Moreover, delta receptor agonists and enkephalinase inhibitors have an antidepressant-like effect in animal studies (Tejedor-Real et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Running has Differential Effects on NPY, Opiates, and Cell Proliferation in an Animal Model of Depression and Controls

Bjørnebekk

Mathé

Brené

2005

Neuropsychopharmacol

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“…In addition, compounds that activated the delta-opioid receptor have been shown to have antidepressant-like properties in a number of animal models. The selective delta-opioid agonist Tyr-D-Ser-(O-C(CH 3 ) 3 )-Gly-Phe-Leu-Thr-(O-C(CH 3 ) 3 (BUBU) produced antidepressant-like effects in the learned helplessness model of depression (Tejedor-Real et al 1998). Similarly, increasing levels of endogenous delta-opioid peptides with enkephalinase inhibitors such as RB101 revealed antidepressant-like effects in models of depression in mice and rats (Baamonde et al 1992;Tejedor-Real et al 1998).…”

Section: Introductionmentioning

confidence: 99%

“…The selective delta-opioid agonist Tyr-D-Ser-(O-C(CH 3 ) 3 )-Gly-Phe-Leu-Thr-(O-C(CH 3 ) 3 (BUBU) produced antidepressant-like effects in the learned helplessness model of depression (Tejedor-Real et al 1998). Similarly, increasing levels of endogenous delta-opioid peptides with enkephalinase inhibitors such as RB101 revealed antidepressant-like effects in models of depression in mice and rats (Baamonde et al 1992;Tejedor-Real et al 1998). More recently, the nonpeptidic delta-opioid agonists SNC80 and (+)BW373U86 displayed naltrindole (NTI)-sensitive antidepressant-like properties in the forced swim test in rats (e.g., Broom et al 2002a;Jutkiewicz et al 2004).…”

Section: Introductionmentioning

confidence: 99%

Separation of the convulsions and antidepressant-like effects produced by the delta-opioid agonist SNC80 in rats

et al. 2005

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Rationale-Delta-opioid agonists produce a number of behavioral effects, including convulsions, anti-nociception, locomotor stimulation, and antidepressant-like effects. The development of these compounds as treatments for depression is limited by their convulsive effects. Therefore, determining how to separate the convulsive and antidepressant-like characteristics of these compounds is essential for their potential clinical use.Objective-The present study tests the hypothesis that the rate of delta-opioid agonist administration greatly contributes to the convulsive properties, but not the anti-depressant-like effects, of delta-opioid agonists.Materials and methods-The delta-opioid agonist SNC80 (1, 3.2, and 10 mg kg −1 or vehicle) was administered to Sprague-Dawley rats by intravenous infusion over different durations of time (20 s, 20, or 60 min). Convulsions were measured by observation prior to determining antidepressantlike effects in the forced swim test.Results-Slowing the rate of SNC80 administration minimized delta agonist-induced convulsions without altering the effects of SNC80 in the forced swim test.Conclusions-These data suggest that delta agonist-induced antidepressant properties are independent of convulsive effects, and that it may be possible to eliminate the convulsions produced by delta agonists, further promoting their potential clinical utility.

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“…Interestingly, the enkephalinase inhibitors RB101 and BL-2401 exert an antidepressant-like action in a learned helplessness assay in rats, presumably by inhibiting the degradation of endogenous opioids (Baamonde et al 1992;Kita et al 1997). The effect of RB101 was reversed by the ␦ -opioid receptor antagonist nal-trindole implicating the ␦ -opioid receptor in its mechanism of action (Tejedor-Real et al 1998). Conversely, chronic administration of the opioid antagonist naltrexone induced a depression-like syndrome indicating a general role for opioid systems in depression (Hollister et al 1981;open, placebo-controlled study).…”

mentioning

confidence: 99%

Nonpeptidic δ-opioid Receptor Agonists Reduce Immobility in the Forced Swim Assay in Rats

Broom

Jutkiewicz

Folk³

et al. 2002

Neuropsychopharmacology

166

122

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The present study examined the effect of opioid receptor agonists in the rat forced swim assay. The ␦ -opioid receptor agonists SNC80 (( ϩ )-4-[( ␣ R)-␣ -((2S,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,Ndiethylbenzamide) and ( 7 ␣ ,5]classes of compounds have also been investigated and have potential antidepressant activity. One such class of agents is the opioids. Studies have been performed using a variety of different opioid system-enhancing agents that suggest an antidepressant role for opioid agonists. Such studies have demonstrated antidepressant activity with the opioid ligand cyclazocine (Fink et al. 1970; open, placebo-controlled study) and with the opioid peptide ␤ -endorphin (Kline et al. 1977; open study). Interestingly, the enkephalinase inhibitors RB101 and BL-2401 exert an antidepressant-like action in a learned helplessness assay in rats, presumably by inhibiting the degradation of endogenous opioids (Baamonde et al. 1992;Kita et al. 1997). The effect of RB101 was reversed by the ␦ -opioid receptor antagonist nal-

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Involvement of δ-opioid receptors in the effects induced by endogenous enkephalins on learned helplessness model

Cited by 95 publications

References 51 publications

Running has Differential Effects on NPY, Opiates, and Cell Proliferation in an Animal Model of Depression and Controls

Running has Differential Effects on NPY, Opiates, and Cell Proliferation in an Animal Model of Depression and Controls

Separation of the convulsions and antidepressant-like effects produced by the delta-opioid agonist SNC80 in rats

Nonpeptidic δ-opioid Receptor Agonists Reduce Immobility in the Forced Swim Assay in Rats

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