Chronic antidepressant administration decreases the expression of tyrosine hydroxylase in the rat locus coeruleus.
AUTOR(ES)
Nestler, E J
RESUMO
Regulation of tyrosine hydroxylase expression by antidepressant treatments was investigated in the locus coeruleus (LC), the major noradrenergic nucleus in brain. Rats were treated chronically with various antidepressants, and tyrosine hydroxylase levels were measured in the LC by immunoblot analysis. Representatives of all major classes of antidepressant medication-including imipramine, nortriptyline, tranylcypromine, fluvoxamine, fluoxetine, bupropion, iprindole, and electroconvulsive seizures-were found to decrease levels of tyrosine hydroxylase immunoreactivity by 40-70% in the LC. Decreased levels of enzyme immunoreactivity were shown to be associated with equivalent decreases in enzyme mRNA levels. Antidepressant regulation of LC tyrosine hydroxylase appeared specific to these compounds, inasmuch as chronic treatment of rats with representatives of other classes of psychotropic drugs, including haloperidol, diazepam, clonidine, cocaine, and morphine, failed to decrease levels of this protein. The results demonstrate that chronic antidepressants dramatically downregulate the expression of tyrosine hydroxylase in the LC and raise the possibility that such regulation of the enzyme represents an adaptive response of LC neurons to antidepressants that mediates some of their therapeutic actions in depression and/or other psychiatric disturbances.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=54779Documentos Relacionados
- Stress and antidepressants differentially regulate neurotrophin 3 mRNA expression in the locus coeruleus.
- Long-term antidepressant administration alters corticotropin-releasing hormone, tyrosine hydroxylase, and mineralocorticoid receptor gene expression in rat brain. Therapeutic implications.
- Muscarine increases cation conductance and decreases potassium conductance in rat locus coeruleus neurones.
- Synaptic potentials in rat locus coeruleus neurones.
- Hypoxic changes in rat locus coeruleus neurons in vitro.