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The effects of scopolamine and the nootropic drug phenotropil on rat brain neurotransmitter receptors during testing of the conditioned passive avoidance task

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Abstract

We studied the effects of administration of the new nootropic drug phenotropil (N-carbamoylmethyl-4-phenyl-2-pyrrolidone) at a dose of 100 mg/kg on the quantitative characteristics of dopamine (DA), serotonin (5-HT), glutamate (NMDA), GABA-A (BDZ), and acetylcholine (nACh) receptors in rats using the conditioned passive avoidance task (PAT) under normal conditions and during scopolamine-induced amnesia ex vivo. We found that the cholinolytic drug scopolamine induced a substantial increase in the density (B max) of n-choline receptors in the cortex (by 99% as compared to the control) and NMDA receptors in the hippocampus (by 93%). A single administration of phenotropil (100mg/kg, intraperitoneally) abolished the effect of scopolamine and decreased the number of nACh and NMDA receptors by 46% and 14%, respectively. Phenotropil also abolished the effect of scopolamine on the benzodiazepine receptors and dopamine D1 receptors. Scopolamine decreased the density of D1 receptors by 20% and BDZ receptors by 17%, whereas phenotropil increased the density of receptors by 16% and 25%, respectively. Phenotropil considerably increased the density of dopamine D2 and D3 receptors by 29% and 62%, respectively. Scopolamine also increased the density of D3 receptors by 44% as compared to the control. We did not find any changes in the binding characteristics of 5-HT2 receptors during scopolamine-induced amnesia or during phenotropil treatment. These results demonstrate the role of these receptors in the development of scopolamine-induced amnesia and in neurochemical mechanisms of the anti-amnestic effects of phenotropil.

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Correspondence to Yu. Yu. Firstova.

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Original Russian Text © Yu.Yu. Firstova, D.A. Abaimov, I.G. Kapitsa, T.A. Voronina, G.I. Kovalev, 2011, published in Neirokhimiya, 2011, Vol. 28, No. 2, pp. 130–141.

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Firstova, Y.Y., Abaimov, D.A., Kapitsa, I.G. et al. The effects of scopolamine and the nootropic drug phenotropil on rat brain neurotransmitter receptors during testing of the conditioned passive avoidance task. Neurochem. J. 5, 115–125 (2011). https://doi.org/10.1134/S1819712411020048

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