Article

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: 2.59). 07/2002; 446(1-3):97-101. DOI: 10.1016/S0014-2999(02)01760-0
Source: PubMed

ABSTRACT 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.

0 Bookmarks
 · 
44 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Involvement of the dopamine D1 and D2 receptors in the nucleus accumbens (NAc) with interaction between morphine and nicotine on inhibitory avoidance (IA) memory was investigated. A step-through type of inhibitory avoidance tasks was used to assess memory in male Wistar rats. The results showed that subcutaneous (s.c.) administration of morphine (7.5 mg/kg) after training decreased retrieval of IA memory in the animals when tested 24 h later. Pre-test administration of the same dose of morphine significantly reversed the deficiency in retrieval. The results also showed that pre-test administration of nicotine (0.2 and 0.4 mg/kg, s.c.) by itself mimicked the effect of pre-test morphine, and lower doses of nicotine (0.1 and 0.2 mg/kg) also improved the effect of a low dose of morphine (2.5 mg/kg) on retrieval of IA memory. Pre-test intra-NAc administration of the dopamine D1 receptor antagonist, SCH 23390 (0.001 and 0.01 µg/rat), and the dopamine D2 receptor antagonist, sulpiride (0.5 and 1 µg/rat) caused no significant effects on IA memory by themselves, but both prevented reinstatement of the retrieval of IA memory by the effective dose of nicotine (0.4 mg/kg). It can be concluded that the dopaminergic mechanism(s) in the NAc is a crosslink for the effect of morphine and nicotine on reinstatement of retrieval of IA memory impaired by post-training administration of morphine.
    Journal of Psychopharmacology 05/2011; 25(8):1126-33. · 3.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Graphical abstract Novel endomorphin-2 analogs modified by introduction of β-Pro with a phenyl substituent in position 4 were synthesized. Tyr-(3R,4S)-4-Ph-β-Pro-Phe-Phe-NH2 produced antinociceptive and antidepressant-like effect, while the second analog containing (3S,4R)-4-Ph-β-Pro was inactive.
    Bioorganic & Medicinal Chemistry. 01/2014;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The amnesic effect of morphine is well known in the laboratory animals. But, it is unclear that morphine at what times can exactly affect different phases of memory, including acquisition, consolidation, and retrieval. Therefore, we investigated the time profile of morphine's amnesic effect on passive (inhibitory) avoidance learning and memory in male Wistar rats. In order to evaluate the outcomes of pre- and post-training administrations of morphine, the animals were trained in a step-through type of passive avoidance task at various time points, and were tested 24 h after training to measure memory retrieval. The results showed that acquisition of memory was impaired in the animals that received a dose of 7.5 mg/kg of morphine (Intraperitoneally) at 0, 30 min, and 1 h before training, as evidenced by a decrease in step-through latency on the test day. Post-training administrations of morphine at 30 min and 1h, 4h except for the time immediately after training, did not impair memory consolidation. The results also showed that pre-test administrations of morphine at 0 and 30 min before the test, impaired retrieval of inhibitory avoidance memory. Taken together, the results suggest that morphine, when injected at different time points before training, after training, or before testing affects different phases of inhibitory avoidance memory. With regard to the time of injections related to each phase, other experiments can be designed to investigate molecular mechanisms involved in the impairing effect of morphine in each phase.
    Archives of Iranian medicine 01/2013; 16(1):34-7. · 1.22 Impact Factor