103 



sion of responding was reinstated in a dose-dependent manner by higher doses of 

 nicotine (0.35 - 0.65 mg/kg). 



It is unclear whether the development of tolerance to the behaviorally 

 disrupting effects of nicotine is due to altered concentrations of nicotine at 

 the receptor (i.e., dispositional tolerance), to altered sensitivity of nico- 

 tine receptors (i.e., functional/physiological tolerance), or to certaip 



behavioral or environmental factors (Dews, 1978; Schuster,' 1978). A variety of 



■ * 



compounds have been examined with a procedure designed to separate the influ- 



— ■ - - -. - "^ 



ence of behavioral from disposftiona'l and/or physiological mecJftnisms of 



tolerance (Campbell and Seiden, 1973; Carlton and Woglin, 1971; Chen, 1969; 



Harris and Snell, 1980; Le Blanc etal_., 1976; Meltzer and Rosecrans, 1982; 



Murray et al_. , 1977; Woolverton and Balster, 1979). This procedure involves 



the chronic dosing of different groups of subjects either before or after the 



experimental session. The test performance of the group dosed before the 



session is therefore altered by the compound, whereas the performance of the 



group dosed after the session is not altered. Once tolerance develops in the 



group dosed before testing, the group dosed after testing is administered the 



compound presassion as a test for tolerance. If the before group Is found to 



be more tolerant than the after group, then it is implied that factors arising 



from the disruption of the test performance by the compound (and nol^he mere 



repeated administration of the compound) were instrumeataL-in detenntning the 



extent to which tolerance developed. - . , 



While the present study was in progress Hendry and Rosecrans (1982) 



reported using the before/after paradigm to evaluate nicotine tolerance in mice 



responding under an FR 25 schedule of sweetened oilk reinforcement. Acute 



nicotine suppressed responding in a dose-related manner (0.2 - 1.6 mg/kg/s.c). 



