PubMed · 10469602
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A J Parkin. 1999-08-26. Human memory.. https://doi.org/10.1016/s0960-9822(99)80378-9
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The aim of this study was to elucidate the effect caused by the inhibition of histamine catabolism by means of metoprine and the activation of histamine H(1) receptors by selective agonists on learning and memory processes, using a modified method of the mouse passive avoidance test. The administration of scopolamine 1 mg/kg (i. p.) immediately after the training session caused statistically-significant amnesia during the retention trial performed 24 h later. Piracetam (30 mg/kg (i.p.)), used as a positive control, and administered 20 min before the training session, prevented scopolamine-induced memory impairment. The histamine-N-methyltransferase inhibitor, metoprine, (2 and 5 mg/kg (s.c.)) had effects similar to those of this nootropic drug. The highly-selective H(1) receptor agonist, 2-(3-trifluoromethylphenyl)histamine (FMPH) (2.65 and 6.5 microg/mouse (i.c.v.)) and the less selective agonist, 2-thiazolylethylamine (2-TEA) (0.1 and 0.3 microg/mouse (i.c.v.)) both antagonized the scopolamine-induced amnesia significantly and in a dose-related manner. The selective H(1) receptor antagonist, pyrilamine (20 mg/kg (i.p.)), revealed no effect by itself, but significantly prevented the antiamnesic action both that of the H(1) receptor agonists, and that of endogenous histamine, released by metoprine, thus suggesting a cognitive improvement via the activation of H(1) receptors.
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Steroid sulfatase inhibitors can enhance the concentration of the neurosteroid DHEAS in rat brain. Previous studies have demonstrated that the steroid sulfatase inhibitor (p-O-sulfamoyl)-N-tetradecanoyl tyramine (DU-14) could reverse scopolamine induced amnesia in rats in a passive avoidance memory paradigm. The intent of this study was to determine whether chronic pretreatment with DU-14 could reverse scopolamine amnesia and/or enhance spacial memory in the place, probe and cued versions of the Morris water maze (MWM). Rats were divided into four groups and administered IP for 15 days either DU-14 (30.0 mg/Kg) or corn oil (1.0 ml/Kg) vehicle. On training days animals were administered either scopolamine (1.0 mg/Kg) or saline (1.0 ml/Kg). The groups administered DU-14 displayed a significant enhancement in learning and spacial memory in the place version of the MWM, when compared to respective vehicle-scopolamine and vehicle-saline groups. In the probe version, the DU-14-saline group remained in the target quadrant of the maze significantly longer than any of the other groups indicating enhanced retention. In the cued version of the MWM, treatment with DU-14 did not significantly change escape latency suggesting that the steroid sulfatase inhibitor did not alter motivation or locomotion. These results suggest that the chronic administration of steroid sulfatase inhibitors enhance learning and spatial memory in rats.