102 



DEVELOPMENT OF BEHAVIORAL TOLLERANCE FOLLOWING 

 CHRONIC NICOTINE ADMINISTRATION 



Paul C. Mele and Victor J. DeNoble 



It is well documented that tolerance develops to many of the effects of 

 nicotine following its repeated administration. In humans, tolerance to the 

 pressor and subjective effects of intravenously administered nicotine has been 

 reported (Jones ^al_., 1978; Rosenberg et al_.. 1980). In rats and/or mice, 

 tolerance develops to nicotine-induced convulsions (Behrend and Thieves, xJiJ;, 

 electroencephalographic arousal (Hubbard and Gohd, 1975)^ and increases jn 

 corticosterone secretion (Benwell — and Ralfour , 1979; Balfour, 19§p) and -*n- 

 urinary catecholamine levels (Westfall and Brase, 1971). Behavioral iy, toler- 

 ance develops to nicotine-induced suppression of locomotor activity (Behrend 

 and Thieves, 1933; Falkenborn e_t al_., 1981; Hatchel and Collins, 1977; Keenan 

 and Johnson, 1972; Morrison and Stephenson, 1972; Stolerman et al., 1973; 

 1974) and responding maintained by fixed ratio (FR) .schedules of reinforcement 

 (Domino and Lutz, 1973; Dougherty et al_. , 1981; Hendry and Rosecrans, 1982). 

 In contrast, feeding studies suggest that tolerance does not develop to the 

 decreases in body weight and in food and fluid intake produced by nicotine 

 (Baettig et al_. , 1980; Falkenborn etal_., 1981). 



For schedule-controlled responding. Domino and Lutz (1973) reported that 

 .the first administration of 0.25 mg/kg.of nicotine suppressed lever pressing 

 under and FR 15 schedule of water presentation for the majority of a Is minutes 

 test session; recovery of control response rates occurred rather abrubtly 

 towards the end 'of the session. Daily injections of nicotine resulted in a' 

 progressive attentuation of the suppression. By day 15 of chronic dosing only 

 a slight suppression of responding was evident at the start of the session. 

 Dougherty _et al_. , (1981) reported a similar finding using an FR 50 .schedule^ 

 These investigators also demonstrated that once tolerance developed, suppres- 



