Endomorphins 1 and 2 induce amnesia via selective modulation of dopamine receptors in mice

Department of Chemical Pharmacology, Faculty of Pharmacy, Meijo University, 468-8503, Nagoya, Japan.
European Journal of Pharmacology (Impact Factor: 2.53). 07/2002; 446(1-3):97-101. DOI: 10.1016/S0014-2999(02)01760-0
Source: PubMed


The involvement of dopamine receptors in the amnesic effects of the endogenous micro-opioid receptor agonists endomorphins 1 and 2 was investigated by observing step-down type passive avoidance learning in mice. Although the dopamine D1 receptor agonist R(+)-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol hydrochloride (R(+)-SKF38393) (0.05 and 0.1 mg/kg), the dopamine D1 receptor antagonist R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (R(+)-SCH23390) (2.5 and 5 microg/kg) or the dopamine D2 receptor agonist N-n-phenethyl-N-propylethyl-p-(3-hydroxyphenyl)-ethylamine (RU24213) (0.3 and 1 mg/kg) had no significant effects on the endomorphin-1 (10 microg)- or endomorphin-2 (10 microg)-induced decrease in step-down latency of passive avoidance learning, (-)-sulpiride (10 mg/kg), a dopamine D2 receptor antagonist, significantly reversed the decrease in step-down latency evoked by endomorphin-2 (10 microg), but not by endomorphin-1 (10 microg). Taken together, it is likely that stimulation of dopamine D2 receptors results in the endomorphin-2-but not endomorphin-1-induced impairment of passive avoidance learning.

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    • "It has also been demonstrated that endomorphins and the m-opioid receptors are present in the brain regions containing monoamine neurotransmitters (serotonin, dopamine, and noradrenaline), which play a key role in the physiopathology of depressive disorders. In fact, endomorphins have been shown to modulate serotoninergic (Chen et al, 2001; Tao and Auerbach, 2002; Hung et al, 2003), dopaminergic (Chen et al, 2001; Ukai and Lin, 2002; Online publication: 1 June 2006 at Npp060106060062/default.pdf Received 31 January 2006; revised 28 April 2006; accepted 30 May 2006 *Correspondence: "
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    ABSTRACT: Endomorphin-1 (Tyr-Pro-Trp-Phe-NH(2)) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH(2)) are two recently isolated mu-opioid selective peptides with a potent antinociceptive activity, involved in a number of physiological processes, including food intake, vasomotricity, sexual behavior, as well as neuroendocrine and cardiorespiratory functions. The neuroanatomical distribution of endomorphins prompted us to study their antidepressant activity in two animal behavioral models of depression: forced-swimming and tail-suspension tests. In both tests, the intracerebroventricular (i.c.v.) injection of either endomorphin-1 or endomorphin-2 significantly decreased the duration of immobility, interpreted as an expression of 'behavioral despair', which could be related to the depression syndrome. These effects of endomorphins did not result from the stimulation of the animal motor activity. We have also demonstrated that the antidepressant-like effect of endomorphins was antagonized by the universal opioid antagonist, naloxone and the mu-opioid receptor selective antagonist, beta-funaltrexamine. In contrast, this effect was not antagonized by delta- and kappa-opioid receptor selective antagonists, naltrindole and nor-binaltorphimine, respectively. The results of the present study demonstrate that endomorphin-1 and endomorphin-2 produce potent antidepressant-like effects after i.c.v. injection in mice. We may suggest that endomorphins and the mu-opioid receptors might be involved in the physiopathology of depressive disorders, and that the endomorphinergic system could serve as a novel target for the development of antidepressant drugs.
    Neuropsychopharmacology 05/2007; 32(4):813-21. DOI:10.1038/sj.npp.1301149 · 7.05 Impact Factor
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    ABSTRACT: There are several conflicting evidences showing the effect of morphine on learning and memory processes. In the present study the effect of chronic morphine administration on passive avoidance, active avoidance and spatial learning and memory of morphine dependent male rats using Passive Avoidance shuttle box and Morris Water Maze tasks were investigated, respectively. Male rats received morphine sulfate in their drinking water for 21 days. Morphinedependency was assessed by injection of naloxone HCl (2 mg/kg) showing the withdrawal signs. Our results showed that in the passive avoidance experiments although the learning of the morphine dependent group was lower than the sham and control groups, but was not statistically significant. Also no significant difference was observed between the memory retention of these groups. In the 2-way active avoidance task, learning was increased significantly in morphine dependent rats in the first day of training with respect to the sham and control groups. But, there was no significant difference in memory of these three groups. Our data in the Morris Water Maze showed that learning of the dependent group in the 3rd day of training decreased significantly with respect to the sham and control groups. But no significant difference was observed in their memory retention and also in their motor activity. Our results showed that in the male rats, chronic morphine administration decreased spatial learning, but had no effect on spatial memory and motor activity. On the contrary, it facilitated 2-way active avoidance learning but had no effect on active and passive avoidance memory. In conclusion, it seems that the effect of morphine dependency on learning and memory in rats is task dependent and depends on the types of experimental learning and memory paradigms.
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    ABSTRACT: The antitussive effects of endomorphin-1 and endomorphin-2, endogenous mu-opioid receptor agonists, on capsaicin-induced coughs were examined in mice. Endomorphin-2, at doses of 3, 10 and 30 microg, i.c.v., dose-dependently inhibited the number of capsaicin-induced coughs. However, the same doses (3, 10 and 30 microg) of endomorphin-1 injected with i.c.v. had no significant effects on the number of capsaicin-induced coughs. The antitussive effect of endomorphin-2 was significantly reduced by beta-funaltrexamine, a mu(1)/mu(2)-opioid receptor antagonist, but not naloxonazine, a selective mu(1)-opioid receptor antagonist. Furthermore, the antitussive effect of endomorphin-2 was also partially but significantly reduced by nor-binaltorphimine, a selective kappa-opioid receptor antagonist. These results indicate that the administration of the endogenous mu-opioid ligand endomorphin-2, but not endomorphin-1, into the brain produces an antitussive effect via mainly naloxonazine-insensitive mu-opioid receptors, namely mu(2)-opioid receptors and partially kappa-opioid receptors.
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