Behavioral effects of nicotine, amphetamine and cocaine under a fixed-interval schedule of food reinforcement in rats chronically exposed to caffeine

Epidemiological surveys demonstrate that caffeine, the main psychoactive in gredient of coffee, is a positive correlate in drug abuse. To characterize the behavioral nature of caffeine interactions with other psychomotor stimu lants, we examined the effects of chronic caffeine exposure on the behavior al responses to nicotine, amphetamine, cocaine, the selective D-1 agonist S KF-82958 and the selective D-2 receptor agonist NPA, in rats responding und er a fixed interval (FI) schedule of food reinforcement. Following stabiliz ation of rates and temporal patterns of responding (mathematically expresse d as quarter-life values, QL), twenty-one Sprague-Dawley rats responding un der a 5-min FI schedule of food reinforcement were divided into two groups; one (twelve rats) maintained on tap water (control) and the other (nine ra ts) on caffeine (3 mg/ml added to the drinking water). Following the substi tution of caffeine solution for tap water, behavior was temporarily disrupt ed as evidenced by decreases in responding and QL values which reached a ma ximum after 72 h (rate 60% and QL 30% below baseline levels), Rats develope d complete tolerance to these effects of caffeine over 5 days of caffeine e xposure. After response rate and QL values stabilized, effects of drugs wer e evaluated. Nicotine (0.01-1.0 mg/kg; SC), amphetamine (0.1-5.6; IP), and cocaine (1.0-17; IP) each produced biphasic dose-dependent changes in respo nse rate with maximum increases in response rate following intermediate dos es and decreases in response rates following higher doses. The increase in rates of responding produced by amphetamine or cocaine (but not nicotine) w ere greater (P<0.05) in caffeine-drinking than in water-drinking rats. Both SKF-82958 (0.001-0.3 mg/kg; IP) and NPA (0.0001-0.1; IP) produced only dos e-dependent decreases in rates of responding. Caffeine-drinking rats were l ess sensitive to the rate-depressant effects of SKF-82958 (P<0.05) than wat er-drinking rats. However, similar changes (P>0.05) were produced by NPA in both groups. Except for amphetamine, the remaining drugs produced similar (P>0.05) dose-dependent decreases in QL values in water- and caffeine-drink ing rats. Amphetamine produced smaller decreases in QL values in caffeine-d rinking rats than in water-drinking rats (P<0.05). Chronic exposure to caff eine produced complete insurmountable tolerance to the response-rate increa sing (stimulant) effects of acute caffeine (3.0-17 mg/kg; IP) in caffeine-d rinking rats. In conclusion, our study revealed that chronic caffeine expos ure potentiates the behavioral response to amphetamine and cocaine but not to that of nicotine in rats responding under a FI schedule of food reinforc ement. Thus, it is likely that these effects are mediated through different pharmacological mechanisms.