In single-unit in-vivo recording experiments in anesthetized rats, i.v. injection of 0.2 mg/kg nicotine enhanced firing rate (Fig.5A: F(6,7)=6.99, p<.0001;) and burst firing (Fig. 5B: F(6,7)=2.837; p<.05) of VTA dopamine neurons that were antidromically identified as projecting to the nucleus accumbens. At doses of WY14643 that significantly reduced nicotine self administration and nicotine-induced reinstatement in the behavioral experiments, WY14643 and methOEA did not alter spontaneous firing rate (Fig. 5A,C; basal mean Hz ±SEM.; controls: 3.24±0.2; WY14643 20 mg/kg: 3.2±0.6; WY14643 40 mg/kg: 3.3±0.6; methOEA 5 mg/kg: 3.18±0.5; MK886+WY1464340 mg/kg: 3.6±0.8; methOEA 10 mg/kg: 3.11±0.4) or burst firing (Fig. 5B,D; basal mean % of spikes/bursts ± SEM; controls: 12.9±3.72; WY14643 20 mg/kg: 13.6±9.88; WY14643 40 mg/kg: 15.8±6.1; MK886+WY1464340 mg/kg: 8.0±6.4; methOEA 5 mg/kg: 8.7±3.57; methOEA 10 mg/kg: 8.9±1.61) of VTA dopamine neurons when given alone. However, when given before nicotine, 20 mg/kg of WY14643 partially blocked and 40 mg/kg of WY14643 completely blocked nicotine-induced excitation of dopamine neurons (Fig. 5A,B: effect of WY14643 on firing rate, F(1,48)=20.36, p<.001; and burst firing, F(1,48)=5.98, p<.05). Intravenous administration of methOEA (5 and 10 mg/kg)
