Selective activation of 5-HT2C receptors stimulates GABA-ergic function in the rat substantia nigra pars reticulata: A combined in vivo electrophysiological and neurochemical study

Mechanisms Contributing to the Phase-Dependent Regulation of Neurogenesis by the Novel Antidepressant, Agomelatine, in the Adult Rat Hippocampus

“…Wood et al, 2001;Berg et al, 2006;Dekeyne et al, 2008;Chanrion et al, 2008;Millan MJ unpublished observations). The notion that inverse agonism is required for enhancing proliferation in the VH is supported by evidence that certain cerebral populations of 5-HT 2C receptors are constitutively active (Berg et al, 2005), including sites tonically inhibitory, through GABAergic interneurones, to ascending dopaminergic or noradrenergic systems that are known to increase cell proliferation (Invernizzi et al, 2007;Hoglinger et al, 2004;Kulkarni et al, 2002;Millan et al, 2008;Aloyo et al, 2009). However, the interpretation of these data is also complicated by the fact that constitutive activity at 5-HT 2C sites is regulated by mRNA editing that differs between brain regions; extensively edited 5-HT 2C receptor isoforms being constitutively silent (Burns et al, 1997;Sanders-Bush et al, 2003).…”

Serotonin modulation of the basal ganglia circuitry: therapeutic implication for Parkinson's disease and other motor disorders

“…The above experimental evidence, although underlining a pivotal role for the 5-HT 2 receptor subtype in the modulation of SNr neurons, does not discriminate the involvement of different subtypes. We have tried to answer this question, and consistent with the aforementioned evidence, we showed that selective 5-HT 2C activation excites SNr neurons in vivo (Di Giovanni et al, 2001;Invernizzi et al, 2007). This effect was evident after both systemic administration and local microiontophoretic application of mCPP and Ro 60-0175 (Di Giovanni et al, 2001;Invernizzi et al, 2007).…”

“…Thus, mCPP caused a marked excitation of presumed SNr projection neurons but did not modify the SNr interneuron firing discharge (Di Giovanni et al, 2001). These data have been confirmed using Ro 60-0175, the most selective agonist to date, which caused excitation only in half of the SNr neurons recorded, although no information about the territory of their innervations was investigated (Invernizzi et al, 2007). Nevertheless, it is most likely that the SNr neurons excited by the 5-HT 2C agonist Ro 60-0175 are the P(0)-projecting neurons that responded to mCPP treatment (Di Giovanni et al, 2001).…”

“…We have tried to answer this question, and consistent with the aforementioned evidence, we showed that selective 5-HT 2C activation excites SNr neurons in vivo (Di Giovanni et al, 2001;Invernizzi et al, 2007). This effect was evident after both systemic administration and local microiontophoretic application of mCPP and Ro 60-0175 (Di Giovanni et al, 2001;Invernizzi et al, 2007). As further confirmation of a selective activation of 5-HT 2C receptors, excitatory effects of mCPP and Ro 60-0175 were blocked by pretretment with SB 242084 and SB 243213, potent and selective 5-HT 2C antagonists.…”

“…On the other hand, local application of SB 243213 into the SNr only partially blocked Ro 60-0175-induced GABA release. This suggests that the control exerted by 5-HT 2C receptors on extracellular GABA in the SNr involves both intra-and extranigral components, such as the striatonigral pathway (Invernizzi et al, 2007). Based on our in vivo (Di Giovanni et al, 2001;Invernizzi et al, 2007) and in vitro (Rick et al, 1995;Stanford and Lacey, 1996;Gongora-Alfaro et al, 1997) evidence, it is possible to speculate that 5-HT released in vivo elicits a direct excitatory response in a discrete population of SNr neurons, probably resulting in the expression of 5-HT 2C , which in turn inhibits a greater number of neighbouring SNr cells through GABA release from their extensive axon collaterals (Mailly et al, 2003;Invernizzi et al, 2007).…”