In-vivo microdialysis experiments in freely-moving rats showed that systemic injection of 0.4 mg/kg nicotine increased extracellular dopamine levels in the nucleus accumbens shell by ∼100% (Fig. 6A: F(12,48)=16.23, p<.0001; Fig. 6B: F(13,65)=58.61; p<.0001). WY14643 alone did not alter dopamine levels, but it significantly reduced nicotine-induced elevations in dopamine levels in a dose-related manner (Fig. 6A: time–treatment interaction, F(18,108)=3.01, p<.001; basal level, expressed as mean fmoles/10 μL sample ±SEM. for controls: 31±2.7; WY14643 40 mg/kg: 31.8 ± 5.2;). Administration of methOEA also did not alter dopamine levels by itself (Fig. 6D), but markedly reduced nicotine-induced elevations in dopamine levels (Fig. 6B: time–treatment interaction, F(26,169)=5.95, p<.0001). The PPAR-α antagonist MK886 had no effect when given alone but completely reversed WY14643's (40 mg/kg) blockade of nicotine-induced elevations in dopamine levels (Fig. 6C: time–treatment interaction, F(26,169)=4.06, p<.05). Similarly, MK866 prevented the effects of 10 mg/kg of methOEA (Fig. 6D: time–treatment interaction, F(28,182)=3.06, p<.01). In contrast, WY14643 did not alter the effects of cocaine on dopamine levels in the nucleus accumbens shell. Basal levels of dopamine in dialysates, expressed as mean fmoles/10 μL sample ±
