112 



than that found on day 31 of chronic dosing {p<.05). This indicates that some 

 tolerance to (-)-nicotine also developed with postsession administration. 



In the before group, response rates during the first six minutes of the 

 session on day 1 of chronic dosing were markedly suppressed to 7.7 ± 4.8% of 

 control levels. This was similar to the response rate reduction to 3.6 ± 2.6% 

 of control found with .8 mg/kg of {-)-nicotine administered a'cutely r Mea t 

 rates of responding increased gradually across sessions of chronic dosing jnd 

 were relatively stable fr om sessions 2 1 to 30 at eo'^to 74% ^f control. 

 Responding in the after group was unaffected by the postsession adimni strati on 

 of nicotine except for several sessions in which rates were slightly decreased 

 {days 7 and 9) or increased (day 26). On day 31, presession administration of 

 nicotine reduced response rates during minutes 0-5 of the session in the before 

 group to 68.1 ± 13.7% and in the after group to 17.7 ± 4.7% of control values; 

 this difference, was statistically significant (p<.05). Nicotine produced 

 slightly though significantly (p<.05) smaller decrease in response rates in the 

 after group on day 31 than it did initially before chronic dosing; response 

 rates were reduced initially to 3.2 ± 1.7% of control levels (Figure 1). 



For approximately 70 additional days the before/after dosing regimen was 

 continued. Ov^r this period the overall response rate of both groups increased 

 slightly and stabilized such that the before group's mean rate wa^at about 

 100% and the after group's mean rate was at abouf'lZCJF of control levels 

 (Figure 2, top). Responding during the first six minutes of the session in the 

 before group continued to be suppressed throughout chronic dosing with the 

 average nicotine rate at about 80% of the mean control rate. 



The nicotine dose-effect functions determined during chronic dosing are 

 presented in Figure 1 (open circles). Compared to the initial dose-effect 

 functions, response rates in both groups of rats were decreased less by all 



