| First Author | Kim DS | Year | 2000 |
| Journal | J Neurosci | Volume | 20 |
| Issue | 12 | Pages | 4405-13 |
| PubMed ID | 10844009 | Mgi Jnum | J:120532 |
| Mgi Id | MGI:3706735 | Doi | 10.1523/JNEUROSCI.20-12-04405.2000 |
| Citation | Kim DS, et al. (2000) Dopamine-deficient mice are hypersensitive to dopamine receptor agonists. J Neurosci 20(12):4405-13 |
| abstractText | Dopamine-deficient (DA-/-) mice were created by targeted inactivation of the tyrosine hydroxylase gene in dopaminergic neurons. The locomotor activity response of these mutants to dopamine D1 or D2 receptor agonists and l-3,4-dihydroxyphenylalanine (l-DOPA) was 3- to 13-fold greater than the response elicited from wild-type mice. The enhanced sensitivity of DA-/- mice to agonists was independent of changes in steady-state levels of dopamine receptors and the presynaptic dopamine transporter as measured by ligand binding. The acute behavioral response of DA-/- mice to a dopamine D1 receptor agonist was correlated with c-fos induction in the striatum, a brain nucleus that receives dense dopaminergic input. Chronic replacement of dopamine to DA-/- mice by repeated l-DOPA administration over 4 d relieved the hypersensitivity of DA-/- mutants in terms of induction of both locomotion and striatal c-fos expression. The results suggest that the chronic presence of dopaminergic neurotransmission is required to dampen the intracellular signaling response of striatal neurons. |
