Caffeine Induces a Stimulant Effect and Increases Dopamine Release in the Nucleus Accumbens Shell Through the Pulmonary Inhalation Route of Administration in Rats

Abstract

Oral, intraperitoneal, or intravenous have been the common routes of administration used to study the behavioral and neurochemical pharmacology of caffeine, one of the most widely used psychoactive substances worldwide. We have reported that caffeine is an active adulterant frequently found in coca-paste (CP)-seized samples, a highly addictive form of smokable cocaine. The role of caffeine in the psychostimulant and neurochemical effects induced by CP remains under study. No preclinical animal studies have been performed so far to characterize the effects of caffeine when it is administered through the pulmonary inhalation route. Caffeine (10, 25, and 50 mg) was volatilized and rats were exposed to one inhalation session of its vapor. The stimulant effect was automatically recorded and plasmatic levels of caffeine were measured. Caffeine capability (50 mg) to increase extracellular dopamine (DA) levels in nucleus accumbens shell was also studied by in vivo microdialysis in non-anesthetized animals. A dose-dependent stimulant effect induced by volatilized caffeine was observed and this effect was directly related with caffeine plasmatic levels. A significant increase in the extracellular DA was achieved after 50 mg of volatilized caffeine exposure. This is the first report showing pharmacological acute effects of caffeine through the pulmonary inhalation route of administration and suggests that this could be a condition under which caffeine can elevate its weak reinforcing effect and even enhance the psychostimulant effect and abuse liability of smokable adulterated psychostimulant drugs.

Multimodal neurocognitive markers of interoceptive tuning in smoked cocaine

“…As observed by the Organization of American States (OAS) and by the United Nations Office on Drugs and Crime (UNODC), experimental research on its effects is scarce. Compared to CC, this basic form has earlier and stronger addictive properties [21], due to smoke inhalation as the administration route [22] and the presence of active adulterants [21,22] and other coca alkaloids [23]. Such higher propensity to dependence [24] results in relatively poor therapeutic outcomes [25].…”

Cocaina base en Chile, 10 años de análisis

“…La cafeína es conocida por sus propiedades estimulantes, debido a su capacidad de interactuar con la neurotransmisión química del cerebro en diversas áreas, promoviendo funciones tales como vigilia, atención, estado de ánimo y excitación motora; principalmente operando a nivel del bloqueo de receptores específicos para la adenosina (22). Recientemente un grupo de investigadores de Uruguay ha establecido mediante estudios en animales que la cafeína provoca un efecto estimulante debido al aumento en la liberación de dopamina en el Núcleo Acumbens cuando se emplea como vía de administración la inhalación de vapores de cafeína y cocaína base (23). Estos hallazgos explican lo reportado en diversos estudios donde señalan la cafeína como el principal adulterante encontrado en las incautaciones de cocaína base, ya sea en América o Europa, convirtiéndose en el más empleado por quienes comercializan cocaína base adulterada (24,25).…”

Dopamine, behavior, and addiction

“…A dopamine antagonist injected into the shell of the ventral striatum blocks these place preferences, whereas the antagonist injected into the core of the ventral striatum blocks the conditioned aversive effects [165]. Volatized, inhaled caffeine increases extracellular dopamine levels in the nucleus accumbens shell [166]. The mechanism by which caffeine does so is not clear.…”