HT2C Receptors and Cholinergic Neurons

In our studies on the distribution of 5-HT2C receptor mRNA in the Macaca brain (Lopez-Gimenez et al. 2001a) we remarked that several regions where cholinergic cell groups are located also contained mRNA for 5-HT2C receptor. These regions of codistribution include several forebrain areas [medial septal nucleus (cholinergic group Ch1), vertical nucleus of diagonal band (Ch2), horizontal nucleus of diagonal band (Ch3), and nucleus basalis of Meynert (Ch4)], several mesencephalic nuclei [pedunculopontine nucleus (Ch5), laterodorsal tegmental nucleus (Ch6), parabig-eminal nucleus (Ch8), oculomotor and trochlear nuclei], and motor nuclei of the brainstem cranial nerve. This correspondence is also observed between the distribution of 5-HT2A receptor mRNA (Lopez-Gimenez et al. 2001b) and several mesen-cephalic and brainstem cholinergic cell groups, particularly in the latter region where the different cranial nerve motor nuclei are highly enriched in both 5-HT2A receptor mRNA and ChAT mRNA. 2A

Fig. 2.2 Cellular visualization of 5-HT2C receptors mRNA in the cingulate cortex. (a) Macroscopic visualization of 5-HT2C receptor mRNA in the mouse coronal section. The inset in (a), corresponding to the cingulate cortex, is shown at higher magnification in (b). (b) Cellular localization of 5-HT2C receptors mRNA (labeled with 33P, black silver grains) in the cells of cingulate cortical layers. GABAergic cells (GAD mRNA expressing cells seen as a brown precipitate) do not display 5-HT2C receptor mRNA hybridization signal. Scale bars: (a) 1 mm; (b) 20 mm

Fig. 2.2 Cellular visualization of 5-HT2C receptors mRNA in the cingulate cortex. (a) Macroscopic visualization of 5-HT2C receptor mRNA in the mouse coronal section. The inset in (a), corresponding to the cingulate cortex, is shown at higher magnification in (b). (b) Cellular localization of 5-HT2C receptors mRNA (labeled with 33P, black silver grains) in the cells of cingulate cortical layers. GABAergic cells (GAD mRNA expressing cells seen as a brown precipitate) do not display 5-HT2C receptor mRNA hybridization signal. Scale bars: (a) 1 mm; (b) 20 mm

In fact, the interaction of cholinergic and serotonergic systems has been extensively studied, especially those aspects relating to the modulation of central cholin-ergic function by serotonin and its possible cognitive implications (See the review in Cassel and Jeltsch (1995)). Regarding 5-HT2C receptors and cholinergic function, several microdialysis studies carried out in rat brain showed the effect of 1-(3-chlo-rophenyl)piperazine (mCPP) (an unselective 5-HT2C receptor agonist) on the release of acetylcholine in rat cortex (Zhelyazkova-Savova et al. 1997) and hippocampus (Zhelyazkova-Savova et al. 1999). This effect consisted of an increase of acetylcholine release, which was shown to be mediated by 5-HT2C receptors, especially in the case of the cortex, providing corroborating evidence that the effect was produced particularly via the nucleus basalis magnocellularis (Zhelyazkova-Savova et al. 1997).

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