Caffeine enhances and accelerates the expression of sensitization induced by coca paste indicating its relevance as a main adulterant

Background and Objectives: Caffeine is an active adulterant found in several drugs of abuse including coca paste (CP). We had previously demonstrated that caffeine potentiated the acute stimulant effect induced by CP seized samples. The role of caffeine in the expression of sensitization elicited by a CP seized sample (CP1) was here evaluated. Methods: CP1 (equivalent dose of 10 mg/kg of cocaine), cocaine (pure, 10 mg/kg), a combination of cocaine 10 mg/kg plus caffeine 2.5 mg/kg (CP1-surrogate) and saline (control) were intraperitoneally injected in male rats under two different sensitization schedules. Ambulatory locomotion was recorded in 58 animals. Results: After five daily CP1 injections and 5 days of withdrawal, CP1-challenged animals displayed a more robust sensitization than cocaine-treated animals. When a 3 injections-regime of CP1- surrogate or cocaine was assayed, only CP1-surrogate was able to elicit sensitization. Discussion and Conclusions: Caffeine enhances and accelerates the CP1-induced sensitization. Scientific Significance: Results may shed light on the fast and high dependence observed in CP users.Agencia Nacional de Investigación e InnovaciónSmoked Cocaine in South Cone Countries Grant CICAD-OEA (USA

Caffeine, a common active adulterant of cocaine, enhances the reinforcing effect of cocaine and its motivational value

Rationale: Caffeine is one of the psychoactive substances most widely used as an adulterant in illicit drugs, such as cocaine. Animal studies have demonstrated that caffeine is able to potentiate several cocaine actions, although the enhancement of the cocaine reinforcing property by caffeine is less reported, and the results depend on the paradigms and experimental protocols used. Objectives: We examined the ability of caffeine to enhance the motivational and rewarding properties of cocaine using an intravenous self-administration paradigm in rats. Additionally, the role of caffeine as a primer cue during extinction was evaluated. Methods: In naïve rats, we assessed (1) the ability of the cocaine (0.250–0.125 mg/kg/infusion) and caffeine (0.125–0.0625 mg/kg/infusion) combination to maintain self-administration in fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement compared with cocaine or caffeine alone and (2) the effect of caffeine (0.0625 mg/kg/infusion) in the maintenance of responding in the animals exposed to the combination of the drugs during cocaine extinction. Results: Cocaine combined with caffeine and cocaine alone was self-administered on FR and PR schedules of reinforcement. Interestingly, the breaking point determined for the cocaine + caffeine group was significantly higher than the cocaine group. Moreover, caffeine, that by itself did not maintain self-administration behavior in naïve rats, maintained drug-seeking behavior of rats previously exposed to combinations of cocaine + caffeine. Conclusions: Caffeine enhances the reinforcing effects of cocaine and its motivational value. Our results highlight the role of active adulterants commonly used in cocaine-based illicit street drugs