Figure 3.

The opponent processes of chronic and acute nicotine and the effect of dopamine (DA) antagonism. (a) Separation of the rewarding effects of chronic nicotine from the aversive effects of withdrawal in nicotine-dependent mice, as revealed by a modified place conditioning paradigm for assessing the rewarding effects of nicotine only (Nicotine procedure; n=11), the aversive effects of nicotine withdrawal (Withdrawal procedure; n=14), or both the rewarding effects of nicotine and the aversive effects of withdrawal (Both procedure; n=15). Nicotine-dependent mice conditioned in all three procedures showed a significant motivational response as compared with saline-treated animals (^*p<0.05). (b) α-flu (0.08 mg/kg, i.p.) pretreatment attenuated the motivational response in each of the B (n=16), N (n=12), and W (n=14) procedures, and had no motivational effect in saline-treated mice. (c) Separation of the rewarding effects of chronic nicotine from the aversive effects of withdrawal in nicotine-dependent rats. Significant effects were observed in the Both (n=8) and Withdrawal (n=10) procedures, but not in the Nicotine (n=10) procedure (^*p<0.05) as compared with saline. (d) α-flu (0.1 mg/kg) pretreatment attenuated the Both (n=8) and Withdrawal (n=4) effects. (e) Previously drug naive mice (n=13) administered a single dose of nicotine (1.75 mg/kg, s.c.) and conditioned immediately (0 h) in the B procedure showed a significant conditioned place aversion for the nicotine-paired environment (^*p<0.05). Mice (n=14) conditioned 8 h after acute nicotine administration showed a significant preference for the nicotine-paired environment (^*p<0.05). Mice conditioned 4 or 12 h after nicotine administration showed no significant effect. Data represent means±SEM.