Abstract：
:It has been proposed that glutamatergic and dopaminergic systems are functionally opposed in their regulation of striatal output. The present study tested the effects of drugs that enhance AMPA-receptor-mediated glutamatergic transmission (ampakines) for their effects on dopamine-related alterations in cortical activity and locomotor behavior. Rats with unilateral 6-hydroxydopamine lesions of the ascending nigro-striatal dopamine system were sensitized to methamphetamine and then tested for methamphetamine-induced circling behavior in the presence and absence of ampakines CX546 and CX614. Both ampakines produced rapid, dose-dependent reductions in circling that were evident within 15 min and sustained through 1 h of behavioral testing. In situ hybridization maps of c-fos mRNA expression showed that in the intact hemisphere, ampakine cotreatment markedly increased c-fos expression in parietal, sensori-motor neocortex above that found in rats treated with methamphetamine alone. Ampakine cotreatment did not augment c-fos expression in frontal, sensori-motor cortex or striatum. Still larger ampakine-elicited effects were obtained in parietal cortex of the dopamine-depleted hemisphere where labeling densities were increased by approximately 60% above values found in methamphetamine-alone rats. With these effects, the hemispheric asymmetry of cortical activation was less pronounced in the ampakine-cotreatment group as compared with the methamphetamine-alone group. These results indicate that positive modulation of AMPA-type glutamate receptors 1) can offset behavioral disturbances arising from sensitized dopamine receptors and 2) increases aggregate neuronal activity in a regionally selective manner that is probably dependent upon behavioral demands.
journal_name
Neurosciencejournal_title
Neuroscienceauthors
Hess US,Whalen SP,Sandoval LM,Lynch G,Gall CMdoi
10.1016/s0306-4522(03)00423-8keywords:
subject
Has Abstractpub_date
2003-01-01 00:00:00pages
509-21issue
2eissn
0306-4522issn
1873-7544pii
S0306452203004238journal_volume
121pub_type
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