Regional differences in the ability of caffeine to affect haloperidol-induced striatal c-fos mRNA expression in the rat.
By using in situ hybridisation we examined the acute effects of caffeine on haloperidol-induced c-fos mRNA in rat striatum. A homogeneous induction of striatal c-fos mRNA was found 30 min after injection of haloperidol (1 mg kg(-1)). At this timepoint caffeine (40 mg kg(-1)) did not affect c-fos mRNA in striatum but caused a significant increase of this gene in the somatosensory cortex. When caffeine was injected together with haloperidol c-fos mRNA was reduced in the medial part of the striatum, but enhanced in the caudal part. Similar region-specific effects of caffeine were observed on c-fos mRNA induced by the selective dopamine D2 antagonist raclopride (0.5 mg kg(-1)). Both haloperidol and raclopride counteracted caffeine-induced c-fos mRNA expression in somatosensory cortex. By contrast no significant interactions between caffeine and the dopamine D1 antagonist SCH 23390 (0.5 mg kg(-1)) on striatal c-fos mRNA expression were observed. The present data show that caffeine modulates c-fos mRNA induced by dopamine D2 receptor antagonism differentially in sensorimotor and limbic-related areas of striatum. It is suggested that this could depend upon a different action of caffeine on the cortical inputs to these two parts of the striatum.
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. Per.Svenningsson@fyfa.ki.se
P
P
Svenningsson
R
R
Nergårdh
B B
BB
Fredholm
D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D016762:Genes, fos / Q000502:physiology*; D006220:Haloperidol / Q000494:pharmacology*; D017403:In Situ Hybridization; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism
D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D002110:Caffeine; D006220:Haloperidol