The effects of scopolamine and the nootropic drug phenotropil on rat brain neurotransmitter receptors during testing of the conditioned passive avoidance task
- First Online:
- 122 Downloads
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 (Bmax) 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.
Keywordsphenotropil nootropic drugs scopolamine PAT dopamine serotonin acetylcholine glutamate benzodiazepines striatum frontral cortex hippocampus
Unable to display preview. Download preview PDF.
- 1.Akhapkina, V.N., Fenotropil. Sb. St., 2007, pp. 6–14.Google Scholar
- 2.Filippova, S.Yu., Aleshina, N.V., and Stepanov, V.P., Fenotropil. Sb. St., 2007, pp. 84–87.Google Scholar
- 3.Kovalev, G.I., Akhapkina, V.I., Abaimov, D.A., and Firstova, Yu.Yu., Atmosfera. Nervnye Bolezni, 2007, no. 4, pp. 22–26.Google Scholar
- 4.Kovalev, G.I. Doctorate (Med.) Dissertation [in Russian], Moscow: NII farmakologii im. V.V. Zakusova, 1993.Google Scholar
- 6.Firstova, Yu.Yu., Cand. Sci. (Biol.) Dissertation [in Russian], Moscow: NII farmakologii im. V.V. Zakusova, 2008.Google Scholar
- 7.Kovalev, G.I. and Prikhozhan, A.V., Farmakologiya nootropov. Eksperimental’noe i klinicheskoe izuchenie. Val’dman A.V., Voronina T.A., Eds., Moscow, 1989, pp. 99–104.Google Scholar
- 8.Kovalev, G., Kudrin, V., Zharikov, S., Pogorelov, V., Bogdanov, M., and Guinetdinov, R., Abstr. of Meeting Dopamine-92, Italy, 1992, p. 29.Google Scholar
- 11.Voronina, T.A. and Ostrovskaya, R.U., in Rukovodstvo po eksperimental’nomu (doklinicheskomu) izucheniyu novykh farmakologicheskikh veshchestv (Manual on Experimental (Preclinical) Studies of New Pharmacological Compounds), Moscow, 2000, pp. 153–158.Google Scholar
- 13.Alexander, S.P., Mathie, A., and Peters, J.A., Guide to Receptors and Channels. BJP, 2006, vol. 147, no. 3, p. 146.Google Scholar
- 29.Aramakis, V.B. and Metherate, R., J. Neurosci., 1998, vol. 18, pp. 257–263.Google Scholar