no 



Overall session response rates averaged for the five saline control 

 sessions preceeding chronic (-)-nicotine administration were 2.62 t 0.29 and 

 2.59 ± 0.23 response/sec for the before and after groups, respectively. .These 

 control rates were similar to the control rates occurring previously during 

 acute nicotine dosing (s^ e aba«e). On day 1 of chronic dosing with .8 ng/kg of 

 (-)-nicotine, the overall session response rate for the before group was 

 reduced to 48.6 ± 9.3% of its mean control level {Figure 2, top). This reduc- 

 tion was not significantly different from the reduction to 40.9 ± 7..1> of 

 control found with the s ame dose _ of _ (-)-nicotine previously^administered 

 acutely. Daily dosing with .8 mgAg of (-)-nicotii;e resulted >n a gradual 

 attenuation of the reduction in response rate over the first 10 days (i.e., 

 tolerance). From day 10 to ay 30 overall response rates were reduced to 80- 

 90% of mean control levels. For the group receiving (-)-nicotine after the 

 session, overall response rates did not differ from control values over the 

 first 30 days of chronic dosing. On day 31 both groups received .8 mg/kg of 

 nicotine before and saline after the session. Response rates v/ere reduced by 

 nicotine on day 31 to a significantly greater degree in the after group than in 

 the before group (Student's t-test, p<,05). In the before and after groups, 

 respectively, response rates were reduced to 90.6 ± 9. Si and 62.6 ± 7. 41 of 

 control values on day 31. The reduction in response rate in the before group 

 was significantly less than the reduction observed in the after gro^ (p<.05), 

 suggesting that the before group was more tolerant than the after group to 

 nicotine.' 



To determine whether tolerance had also developed to some degree in the 

 after group, the effects 'of (-)-nicotine on day 31 were compared to those 

 obtained during the initial dose-effect determination. The initial reduction 

 in overall response rates to 40.9 ± 5.0% of control was significantly greater 



