Fig. 6.
Blockade of 5-HT2C receptor signaling restores cocaine-induced locomotion in DAT Val559 mice independent of DA release. Wildtype (WT, n = 6–7), DAT Val559 (n = 5–6), SERT Met172 and DAT Val559/SERT Met172 hybrids (double mutant, n = 7) were injected with cocaine (10 mg/kg, i.p.) and a, b 5-HT and c, d DA elevations in the striatum measured using in vivo microdialysis. Eluates were pooled in 20 min bins and expressed as averages over time (left) or area under the curve (right). Average baseline DA concentration was 3.22 ± 0.60 nM (WT) and 1.56 ± 0.34 nM (DAT Val559). Average baseline 5-HT concentration was 0.082 ± 0.017 nM (WT) and 0.057 ± 0.011 nM (DAT Val559). Total distance traveled in e, g WT (n = 10–12) and f, h DAT Val559 (n = 10–11) mice injected with saline or cocaine (10 mg/kg, i.p.) following a 30 min pre-exposure to saline or SDZ SER-082 (0.5 mg/kg, i.p.). Data are presented in 5 min bins or summed over the 60 min recording period. *P < 0.05, **P < 0.01, ***P < 0.001 vs saline-treated control via Sidak’s or Dunnett’s post-hoc test. #P < 0.001 vs cocaine treated WT mice. ns = not significantly different. Data are presented as mean ± SEM