Figure 3

From: Functional Status of the Serotonin 5-HT2C Receptor (5-HT2CR) Drives Interlocked Phenotypes that Precipitate Relapse-Like Behaviors in Cocaine Dependence

Figure 3

Functional status of the 5-HT2CR is a neuromolecular substrate for inherent impulsive action. Following phenotype identification in two separate cohorts of rats, the one-choice serial reaction time (1-CSRT) task sessions were terminated, and HI and LI rats were retained in their home cages (food restriction was maintained) and killed within 2–3 days for ex vivo neurochemical analyses of 5-HT2CR protein and mRNA. (a) Qualitative (inset) and quantitative demonstration that HI rats expressed lower levels of membrane medial prefrontal cortex (mPFC) 5-HT2CR vs LI rats (*p<0.05 vs LI). (b) There was an inverse correlation between mPFC 5-HT2CR membrane protein levels and premature responding on the 1-CSRT task for individual subjects (r=−0.709; p<0.01). (c) Immunoprecipitation (IP) for postsynaptic density 95 (PSD95) followed by immunoblot (IB) for 5-HT2CR yielded 5-HT2CR immunoreactivity in both HI and LI rats (inset). Synaptosomal 5-HT2CR associated with PSD95 in the mPFC to a greater extent in HI vs LI rats (*p<0.05 vs LI); comparable levels of PSD95 were immunoprecipitated between HI and LI rats (inset). (d) The 5-HT2CR mRNA editing efficiency was significantly different in HI vs LI rats; editing at the E and D sites was higher in HI vs LI rats (*p<0.05). (e) The frequencies of ABD, AEC, ABED, AECD, and ABECD 5-HT2CR mRNA variants were elevated in HI rats compared with LI rats. HI rats expressed higher levels of predicted protein isoforms VNV and VGV vs LI rats (*p<0.05 vs LI). (f) Total mPFC 5-HT2CR mRNA levels as assessed by RT-PCR did not differ between HI and LI rats (n.s.).