Alteration of dopamine D1 receptor-mediated motor inhibition and stimulation during development in rats is associated with distinct patterns of c-fos mRNA expression in the frontal-striatal circuitry.
Dopamine D1 receptors have been implicated in various neurodevelopmental disorders, including attention-deficit/hyperactivity disorder. However, little is known about potential late maturational changes of the motor inhibitory and stimulatory role of these receptors. Here, we investigated the effects of a full and selective D1 receptor agonist, SKF-81297, on motor activity and expression of the plasticity-associated gene, c-fos, in the prefrontal cortex and striatum of juvenile and adolescent male rats. In general, SKF-81297 produced a biphasic effect on motor activity (locomotor and rearing activity), which consisted of an initial short inhibition followed by a long-lasting stimulation. These effects were dose- and age- dependent. The inhibitory phase was more pronounced in adolescent than in juvenile rats whereas the opposite was true for the stimulatory phase. During the initial inhibitory phase of the drug, c-fos mRNA expression was increased in the prefrontal cortex of juvenile rats but reduced in adolescent rats. There was also an increase in c-fos mRNA expression in the medial-dorsal striatum and olfactory tubercle, which was more evident in juvenile rats. In contrast, during the stimulatory phase, c-fos mRNA expression was increased in both the dorsal and ventral striatum, especially in the nucleus accumbens, as well as in the prefrontal cortex, in both age groups. The increase of c-fos mRNA in the dorsal striatum, however, was more pronounced in juvenile rats. These results indicate the presence of two distinct D1 receptor populations within the frontal-striatal circuitry, which have opposite effects on motor activity, and which have different maturational profiles.
Department of Woman and Child Health, Astrid Lindgren Childrenís Hospital, Q2 : 07, Karolinska Institutet, 171 76, Stockholm, Sweden. Rochellys.Heijtz@home.se
Rochellys
R
Diaz Heijtz
Lena
L
Scott
Hans
H
Forssberg
D000818:Animals; D000831:Animals, Newborn; D001552:Benzazepines / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D005625:Frontal Lobe / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D016762:Genes, fos / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009415:Nerve Net / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000378:metabolism*
D001552:Benzazepines; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; C067113:SK&F 81297