title: Role of dopamine D(1) receptors in caffeine-mediated ERK phosphorylation in the rat brain.
abstract: The aim of this research was to study the role of dopamine D(1) receptors in caffeine elicited ERK phosphorylation in the prefrontal and other cortical (cingulate and motor) and subcortical (shell and core of the nucleus accumbens) regions. To this end, caffeine (3 and 10 mg/kg) was administered before phosphoERK immunohistochemistry. Caffeine dose-dependently increased the number of phosphoERK-positive neurons in the prefrontal and cingulate cortices but not in the secondary motor cortex and in the nucleus accumbens shell and core. The dopamine D(1) receptor antagonist, SCH 39166 (50 microg/kg), fully prevented phosphoERK activation by caffeine (10 mg/kg) in the superficial and deep layers of the prefrontal cortex but failed to prevent it in the cingulate cortex. Given that phosphoERK can be regarded as a postsynaptic marker of neuronal activation, the present results indicate that psychotropic properties of caffeine may result from the activation of prefrontal, via dopamine D(1) receptors, and cingulate cortices. Failure of caffeine to activate ERK in the nucleus accumbens further supports, indirectly, the observation that caffeine fails to activate dopamine transmission in this structure and is consistent with the tenet that caffeine lacks of true addictive properties.
authors.affiliation: Department of Toxicology, University of Cagliari, I-09124 Cagliari, Italy. acquas@unica.it
authors.forename: Elio
authors.initials: E
authors.lastname: Acquas
authors.forename: Stefania
authors.initials: S
authors.lastname: Vinci
authors.forename: Federico
authors.initials: F
authors.lastname: Ibba
authors.forename: Saturnino
authors.initials: S
authors.lastname: Spiga
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: De Luca
authors.forename: Gaetano
authors.initials: G
authors.lastname: Di Chiara
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D002110:Caffeine / Q000008:administration & dosage / Q000494:pharmacology*; D002452:Cell Count; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D001552:Benzazepines; D000697:Central Nervous System Stimulants; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; C058081:ecopipam; D002110:Caffeine; D048049:Extracellular Signal-Regulated MAP Kinases