Study on Action Mechanism of 1‐(4‐Methoxy‐2‐Methylphenyl)Piperazine (MMPP) in Acquisition, Formation, and Consolidation of Memory in Mice

Abstract

In the present study, the mechanism of action of MMPP (1-(4-methoxy-2-methylphenyl) piperazine) in the acquisition (pretraining administration), formation (posttraining administration), and consolidation (pretest administration) of memory was assessed in the passive avoidance test using a short- and long-term memory protocol in mice. MMPP modified avoidance in the acquisition and formation of memory protocols but not in the consolidation protocol. Scopolamine (0.1 mg/kg i.p.), dizocilpine (0.003 mg/kg i.p.), and buspirone (0.1 mg/kg i.p.) completely inhibited MMPP-induced effects on memory acquisition and partially inhibited memory formation in the short-term but not long-term paradigm. This suggested that cholinergic, N-methyl-D-aspartate (NMDA) and 5-hydroxytryptamine-1A (5-HT1A ) receptors were implicated in the MMPP-induced improvements in memory. The sedative, anxiolytic, motor impairment, myorelaxant, and anticonvulsive (pentylenetetrazole-induced seizures) properties of MMPP were also assessed with the compound only showing a nondose-dependent myorelaxation. These results suggest that MMPP can enhance acquisition and formation, but not consolidation, of memory in short-term and long-term protocol via cholinergic, NMDA-glutamatergic, and 5-HT1A receptors.

Effect of <b><i>N</i></b>-Benzylpiperazine, Its Metabolite <b><i>N</i></b>-Benzylethylenediamine, and Its Disubstituted Analogue <b><i>N</i></b>,<b><i>N</i></b>'-Dibenzylpiperazine on the Acquisition, Formation, and Consolidation of Memory in Mice

“…The formation of the memory improved by piracetam ( Fig. 2 ) was in agreement with a previous study [9] . It is clear that BZP has an effect on memory after a single dose; however, the effects on memory after multiple doses are still unknown.…”

“…BZP as well as DBZP, showed a myo-relaxant effect but without any impairment in the motor coordination, whereas BEDA did not. It seems that this effect is characteristic of nootropic compounds, as was observed in previous studies of our group [9,13] . The myo-relaxant effect is a typical effect of benzodiazepines [23] .…”

“…Twenty-four hours after the training period, the animals were placed again in the passive avoidance apparatus and latency was recorded [13] . The results of nootropic effect in this test displayed an U-inverted shape dose-response curve and the doses for maximum response (DMR) were recorded for each compound [9,13] .…”

“…The neuropharmacological profile was performed by the intraperitoneal administration of the DMR of each compounds 30 min before the test: the sedative activity was evaluated in the exploratory cylinder test [9] , the motor coordination on rota-rod test (Rota-rod Treadmills for mice, constant speed model 7600, Ugo Basile; 4 cm diameter,16 rpm), the myo-relaxant effect in the traction test [14] , the anxiogenic effect in the hole board test (Hole Board Apparatus, Ugo Basile 6650) [14], and the locomotor activity in the open field test (IR Actimeter LE8811, Panlab/Harvard Apparatus, MA, USA) [14] using conventional protocols. Diazepam (2.5 mg/kg) was used as reference drug in these tests.…”

“…On the other hand, we previously reported that 1-(4-methoxy-2-methylphenyl)piperazine can enhance the acquisition and formation, but not consolidation of short-term memory and long-term protocol via cholinergic, NMDAglutamatergic, and 5-HT 1A receptors [9] . In contrast, TFMPP and mCPP produce deficits in spatial learning and impair memory consolidation because 5-HT 1B and 5-HT 2A/2C receptors are involved [10] .…”