Figure 5.

Cocaine CPP and abstinence strengthen VP_VGluT2 input to the LHb and VTA_GABA neurons but weaken input to all other targets. A, Left, Timeline of the CPP protocol (from left to right). Mice were habituated to the arena on the first day and then received eight alternating intraperitoneal injections of either cocaine (15 mg/kg) or saline, one injection per day. Control (cocaine-naive) mice received only saline injections. Cocaine was paired with one of the sides, and saline was given on the other side. After conditioning, mice went through 14 d of abstinence from cocaine and then were either tested for preference or used for electrophysiological recordings. Right, Preference for the cocaine-paired side in the cocaine group (C) was significantly higher than zero (one-sample t test, CPP score 0.39 ± 0.26, p = 0.0009) and different from the saline (S) group (p = 0.0019). B–G, Postsynaptic effects. A/N ratios in each target of VP_VGluT2 neurons in saline (full bars) and cocaine-abstinent (open bars) mice. B–F, Cocaine CPP and abstinence decreased the A/N ratio in VP_VGluT2 (B), VP_GABA (C), and VTA_DA (E); generated a nonsignificant decrease in MDT neurons (p = 0.07; F); and did not affect the A/N ratio in VTA_GABA neurons (D). G, In contrast, cocaine CPP and abstinence significantly increased the A/N ratio in the LHb by more than twofold, from 1.55 ± 0.3 to 3.84 ± 1.5. Insets, Representative AMPA (red) and NMDA (blue) currents for each region. NMDA currents normalized between regions to ease comparison. H–L, Presynaptic effects. Cocaine CPP and abstinence decreased the coefficient of variation of evoked EPSCs (CV) and the PPR in both VTA_GABA (H–J) and LHb (K–L) neurons. J, Representative traces for the presynaptic effects of abstinence from cocaine on VP_VGluT2 input to VTA_GABA neurons. All statistical tests are unpaired Student's t tests. The asterisk indicates p < 0.05 when comparing to zero using a one-sample t-test.