119 



week to week. Nicotine-Induced increases remained shorter than those observed 

 during the initial dose-effect determinations. 



DISCUSSION 

 The present results confirm the findings of previous studies which demon- 

 strated that tolerance develops to the behavioral effects of nicotine following 

 chronic administration {e.g., Ntorrison and Stephenson, 1972; Stolc;i.,.i, _^ ^ , 

 1974; Jones et£l_., 1978), including tolerance to the disruption of FR respond* 



ing (Domino and Lutz, 19734-0ou9l>erty -et al . , 1981; Hendry and Ros"fecrans, 



- -- - -^ 



1982). These results extended previous findings by demonstrating that once 

 tolerance develops to a given dose of nicotine, higher doses are required to 

 produce effects quantitatively and qualitatively Similar to those. observed 

 before tolerance developed. Thus, nicotine tolerance was seen here as a shift 

 to the right in the dose-effect functions for measures of response rate reduc- 

 tion and increases in latency to complete the first ratio. There is general 

 agreeinent that tolerance is defined as a lessened effect of a given dose of a 

 compound following its repeated administrationl and by the recoverability of 

 the initial effects by administering higher doses (Krasnegor, 1978). Shifts to 

 the right in complete dose-effect functions have not been reported previously 

 In studies of nicotine tolerance. The alterations in the effects of ^icotine 

 following chronic administration reported here satisfy both criteria^or iden- 

 tifying tolerance. 



The major finding of the present study was that the development of toler- 

 ance to nicotine was highly dependent on factors arising from the nicotine- 

 induced disruption of FR responding, rather than on the mere repeated adminis- 

 tration of nicotine. Thus, behavioral factors appear to be critically Involved 

 in the mechanlsji(s) underlying nicotine tolerance. This is evidenced by the 



