HT2C Receptors and the Dopaminergic Receptors System

Dopaminergic nuclei, such as retrorubral area, substantia nigra pars compacta, ventral tegmental area and periaqueductal gray, and dorsal striatum and nucleus accumbens, express 5-HT2C receptor mRNA (Eberle-Wang et al. 1997; Mengod et al. 1990a; Pompeiano et al. 1994; Ward and Dorsa 1996). Pharmacological activation of 5-HT2C receptors inhibits firing rates of ventral tegmental area neurons and dopamine release within the nucleus accumbens (Prisco et al. 1994; Di Giovanni et al. 1999; Di Matteo et al. 1998). The implication of 5-HT2C receptors in the regulation of nigrostriatal dopaminergic function has been a subject of debate mainly due to controversial results obtained with different 5-HT2C receptor acting molecules (Di Matteo et al. 2001; Porras et al. 2002; De Deurwaerdere et al. 2004; Navailles et al. 2004). Very recently (Abdallah et al. 2009) by using the 5-HT2C receptor null mutant mice, previously generated by Tecott and collaborators (Tecott et al. 1995), it has been studied in a more direct manner the influence of this receptor subtype on functions mediated by the nigrostriatal dopaminergic pathway. Based on results generated by the combination of electrophysiological, pharmacological, neurochemical, and behavioral methods, Abdallah and coworkers have recently described that 5-HT2C receptor null mutant mice displayed (1) an increment in the activity of the dopaminergic neurons of substantia nigra pars compacta, (2) an increment in the extracellular dopamine in the dorsal striatum and nucleus accumbens, (3) increased syntactic grooming chain failures and altered grooming behaviors, and (4) increased sensitivity to the stereotypic behavioral effects following selective dopamine transporter blockade. All these responses occur without phenotypic differences in the elevation of drug-induced striatal extracellular dopamine concentration, suggesting that the loss of 5-HT2C receptor function may be accompanied by enhanced behavioral responses to released dopamine. The phenotypic differences these authors observe in stereotypic behavior following selective stimulation of dopamine D1 receptors with an agonist support this hypothesis. All these findings suggest that 5-HT2C receptors play a significant role in the control of nigrostriatal physiology and behavior.

Defeat Drugs and Live Free

Defeat Drugs and Live Free

Being addicted to drugs is a complicated matter condition that's been specified as a disorder that evidences in the obsessional thinking about and utilization of drugs. It's a matter that might continue to get worse and become disastrous and deadly if left untreated.

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