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



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.



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.



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.



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.
Department of Experimental Neuropharmacology, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay.
José Pedro
JP
Prieto
Department of Experimental Neuropharmacology, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay.
Cecilia
C
Scorza
Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
Gian Pietro
GP
Serra
Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
Valentina
V
Perra
Department of Experimental Neuropharmacology, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay.
Martín
M
Galvalisi
Department of Neurochemistry, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay.
Juan Andrés
JA
Abin-Carriquiry
Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
Giovanna
G
Piras
Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy. valentin@unica.it.
Valentina
V
Valentini
D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D008297:Male; D009042:Motivation / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D012201:Reward; D012646:Self Administration
D000697:Central Nervous System Stimulants; D018765:Dopamine Uptake Inhibitors; D002110:Caffeine; D003042:Cocaine
Addiction; Adulterants; Caffeine; Cocaine; Illicit drugs market; Motivation; Reinforcement; Self-administration