Chronic administration of lithium or other antidepressants increases levels of DARPP-32 in rat frontal cortex.
We studied the chronic actions of lithium on rat brain by investigating its effects on cyclic AMP-dependent protein phosphorylation by use of a back-phosphorylation procedure. We identified one heavily regulated phosphoprotein in frontal cortex as the 32-kDa dopamine- and cyclic AMP-regulated phosphoprotein (DARPP-32). Immunoblot experiments demonstrated that chronic lithium regulation of DARPP-32 back-phosphorylation is associated with equivalent increases in levels of DARPP-32 immunoreactivity. Lithium regulation of DARPP-32 immunoreactivity required chronic drug administration and was not observed in several other brain regions examined. Moreover, chronic administration of the antidepressant imipramine or tranylcypromine produced a similar increase in levels of DARPP-32 in frontal cortex, whereas other types of psychotropic drugs, including haloperidol, morphine, and cocaine, did not influence DARPP-32 levels. Increased levels of DARPP-32 could reflect a common functional effect on frontal cortex of long-term exposure to lithium and some other antidepressant medications, an effect possibly related to the clinical actions of these drugs.
Guitart
X
X
Department of Psychiatry, Yale University School of Medicine, Connecticut Mental Health Center, New Haven 06508.
Nestler
E J
EJ
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D005625:Frontal Lobe / Q000378:metabolism*; D015151:Immunoblotting; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000928:Antidepressive Agents; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D008094:Lithium