Beneficial effects of co-administration of catechol-O-methyltransferase inhibitors and L-dihydroxyphenylalanine in rat models of depression.
The administration of catechol-O-methyltransferase inhibitors alone changed neither the behavior of the rats in two animal models of depression, the forced swimming test (entacapone and tolcapone) or in the learned helplessness paradigm (tolcapone), nor the locomotor activity. L-Dihydroxyphenylalanine (L-DOPA) and carbidopa treatment as such decreased motility but did not improve the behavior in the antidepressant tests. Co-administration of catechol-O-methyltransferase inhibitors and L-DOPA/carbidopa increased the performance of rats in both tests without increasing locomotor activity. Catechol-O-methyltransferase inhibitors could be beneficial as adjunct drugs of L-DOPA not only in Parkinson's disease but also in the coincident depressive illness.
Männistö
P T
PT
University of Helsinki, Department of Pharmacology and Toxicology, Finland.
Lang
A
A
Rauhala
P
P
Vasar
E
E
D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001577:Benzophenones / Q000494:pharmacology / Q000627:therapeutic use*; D002230:Carbidopa / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000494:pharmacology / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy*; D003891:Desipramine / Q000494:pharmacology / Q000627:therapeutic use; D004295:Dihydroxyphenylalanine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D007980:Levodopa / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009570:Nitriles; D009596:Nitrophenols; D051381:Rats; D017208:Rats, Wistar; D013550:Swimming; D000077867:Tolcapone
D001577:Benzophenones; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D009570:Nitriles; D009596:Nitrophenols; D007980:Levodopa; C071192:entacapone; D004295:Dihydroxyphenylalanine; D000077867:Tolcapone; D002230:Carbidopa; D003891:Desipramine