RT Journal Article
SR Electronic
T1 Impact of Serotonin 2C Receptor Null Mutation on Physiology and Behavior Associated with Nigrostriatal Dopamine Pathway Function
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 8156
OP 8165
DO 10.1523/JNEUROSCI.3905-08.2009
VO 29
IS 25
A1 Luna Abdallah
A1 Stephen J. Bonasera
A1 F. Woodward Hopf
A1 Laura O'Dell
A1 Marco Giorgetti
A1 Minke Jongsma
A1 Scott Carra
A1 Massimo Pierucci
A1 Giuseppe Di Giovanni
A1 Ennio Esposito
A1 Loren H. Parsons
A1 Antonello Bonci
A1 Laurence H. Tecott
YR 2009
UL http://www.jneurosci.org/content/29/25/8156.abstract
AB The impact of serotonergic neurotransmission on brain dopaminergic pathways has substantial relevance to many neuropsychiatric disorders. A particularly prominent role has been ascribed to the inhibitory effects of serotonin 2C receptor (5-HT2CR) activation on physiology and behavior mediated by the mesolimbic dopaminergic pathway, particularly in the terminal region of the nucleus accumbens. The influence of this receptor subtype on functions mediated by the nigrostriatal dopaminergic pathway is less clear. Here we report that a null mutation eliminating expression of 5-HT2CRs produces marked alterations in the activity and functional output of this pathway. 5-HT2CR mutant mice displayed increased activity of substantia nigra pars compacta (SNc) dopaminergic neurons, elevated baseline extracellular dopamine concentrations in the dorsal striatum (DSt), alterations in grooming behavior, and enhanced sensitivity to the stereotypic behavioral effects of d-amphetamine and GBR 12909. These psychostimulant responses occurred in the absence of phenotypic differences in drug-induced extracellular dopamine concentration, suggesting a phenotypic alteration in behavioral responses to released dopamine. This was further suggested by enhanced behavioral responses of mutant mice to the D1 receptor agonist SKF 81297. Differences in DSt D1 or D2 receptor expression were not found, nor were differences in medium spiny neuron firing patterns or intrinsic membrane properties following dopamine stimulation. We conclude that 5-HT2CRs regulate nigrostriatal dopaminergic activity and function both at SNc dopaminergic neurons and at a locus downstream of the DSt.