Reduced presynaptic dopamine activity in adolescent dorsal striatum.
Adolescence coincides with symptomatic onset of several psychiatric illnesses including schizophrenia and addiction. Excess limbic dopamine activity has been implicated in these vulnerabilities. We combined molecular and dynamic indices of dopamine neurotransmission to assess dopamine function in adolescent rats in two functionally distinct striatal subregions: nucleus accumbens (NAc) and dorsal striatum (DS). In adolescents, we find an overall reduction in dopamine availability selective to the DS. Dopamine release in the DS, but not in the NAc, was less responsive to amphetamine in adolescents compared to adults. The dopamine transporter (DAT) inhibitor, nomifensine, similarly inhibited basal and amphetamine-induced dopamine release in either regions of both the age groups, suggesting that the reduced effectiveness of amphetamine is not due to differences in DAT function. Furthermore, DAT and vesicular monoamine transporter-2 expressions were similar in the DS and NAc of adolescent rats. In contrast, expression of tyrosine hydroxylase (TH) was reduced in the DS, but not in the NAc, of adolescents compared to adults. Behaviorally, adolescents were less sensitive to amphetamine but more sensitive to a TH inhibitor. These data indicate that, in contrast to the general notion that dopamine is hyperactive in adolescents, there is diminished presynaptic dopamine activity in adolescents that is selective to the DS and may result from attenuated TH activity. Given recent reports of altered dopamine activity in associative/dorsal striatum of individuals at a clinically high risk of psychosis, our data further support the idea that dorsal, as opposed to ventral, regions of the striatum are a locus of vulnerability for psychosis.
Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA.
Marguerite
M
Matthews
Corina
C
Bondi
Gonzalo
G
Torres
Bita
B
Moghaddam
D000367:Age Factors; D000661:Amphetamine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism*; D004347:Drug Interactions; D008124:Locomotion / Q000187:drug effects; D008297:Male; D009627:Nomifensine / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism; D019805:alpha-Methyltyrosine / Q000494:pharmacology
D050483:Dopamine Plasma Membrane Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D009627:Nomifensine; D019805:alpha-Methyltyrosine; D000661:Amphetamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine