Central dopaminergic transmission is selectively increased in the limbic system of rats chronically exposed to antidepressants.
Repeated electroconvulsive shock (ECS) exposure produced a decrease of [3H]SCH 23390 binding sites and a reduced response of adenylate cyclase activity to dopamine D-1 receptor stimulation in the rat limbic area analogous to that previously observed in rats chronically treated with imipramine. These effects were completely prevented by the repeated administration of a small dose of alpha-methyl-p-tyrosine (alpha-MPT), associated with the tricyclic compound. Increased dopaminergic transmission seems to be involved in the mechanism of antidepressant action. Rats chronically treated with imipramine showed a decrease of dihydroxyphenylacetic acid (DOPAC) concentration restricted to the limbic area. Finally, both imipramine and desipramine blocked the uptake of [3H]dopamine in the limbic system with a 100-fold greater potency than that observed in the basal ganglia.
De Montis
G M
GM
Institute of Pharmacology and Biochemical Pathology, University of Cagliari, Italy.
Devoto
P
P
Gessa
G L
GL
Meloni
D
D
Porcella
A
A
Saba
P
P
Serra
G
G
Tagliamonte
A
A
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001552:Benzazepines / Q000378:metabolism; D003342:Corpus Striatum / Q000201:enzymology; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D004597:Electroshock; D008032:Limbic System / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D009435:Synaptic Transmission / Q000187:drug effects*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D019805:alpha-Methyltyrosine
D000928:Antidepressive Agents; D001552:Benzazepines; D008781:Methyltyrosines; D015102:3,4-Dihydroxyphenylacetic Acid; D019805:alpha-Methyltyrosine; D000262:Adenylyl Cyclases; D004298:Dopamine