title: 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.
authors.affiliation: Departamento de Neurofarmacología Experimental, Instituto de Investigaciones Biológicas Clemente Estable, Avenida Italia 3318, 11600, Montevideo, Uruguay.
authors.forename: Martín
authors.initials: M
authors.lastname: Galvalisi
authors.affiliation: Departamento de Neurofarmacología Experimental, Instituto de Investigaciones Biológicas Clemente Estable, Avenida Italia 3318, 11600, Montevideo, Uruguay.
authors.forename: José Pedro
authors.initials: JP
authors.lastname: Prieto
authors.affiliation: Departamento de Neuroquímica, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay.|Plataforma de Servicios Analíticos, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay.
authors.forename: Marcela
authors.initials: M
authors.lastname: Martínez
authors.affiliation: Departamento de Neuroquímica, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay.|Plataforma de Servicios Analíticos, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay.
authors.forename: Juan Andrés
authors.initials: JA
authors.lastname: Abin-Carriquiry
authors.affiliation: Departamento de Neurofarmacología Experimental, Instituto de Investigaciones Biológicas Clemente Estable, Avenida Italia 3318, 11600, Montevideo, Uruguay. scorzacecilia@gmail.com.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Scorza
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D002110:Caffeine / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry; D000697:Central Nervous System Stimulants / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry; D019970:Cocaine-Related Disorders / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D023421:Models, Animal; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism*; D017208:Rats, Wistar; D014835:Volatilization
chemical_list: D000697:Central Nervous System Stimulants; D015259:Dopamine Agents; D002110:Caffeine; D004298:Dopamine
keywords: Adulteration; DA transmission; Drugs of abuse; GC–MS; Pulmonary inhalation