Repeated administration of fluoxetine, desipramine and tranylcypromine increases dopamine D2-like but not D1-like receptor function in the rat.
We tested the effect of repeated treatment (twice daily for 14 days) of rats with the antidepressant drugs fluoxetine, desipramine and tranylcypromine, on the behavioural response to the non-selective dopamine (DA) receptor agonist, apomorphine, the D1-like receptor agonists, SKF 38393 and SKF 81297 and the D2-like receptor agonists, RU 24213 and quinpirole. Agonist-induced behaviour was monitored by automated activity meters and direct observation using a checklist scoring method. Fluoxetine, desipramine and tranylcypromine enhanced (albeit to a varying degree) the behavioural responses to apomorphine (0.75 mg/kg, s.c.), quinpirole (0.25 mg/kg, s.c.) and RU 24213 (0.75 mg/kg, s.c.). In contrast, fluoxetine, desipramine and tranylcypromine did not increase the behavioural responses to SKF 38393 (7.5 mg/kg, s.c.) and SKF 81297 (0.5 mg/kg, s.c.). Finally, fluoxetine, despiramine and tranylcypromine did not modify the behavioural responses to the concomitant administration of SKF 38393 (7.5 mg/kg, s.c.) and quinpirole (0.25 mg/kg, s.c.). Our data suggest that repeated administration of fluoxetine, desipramine and tranylcypromine increases central DA D2-like but not D1-like receptor function.
Ainsworth
K
K
University of Oxford, Department of Clinical Pharmacology, Radcliffe Infirmary, UK.
Smith
S E
SE
Sharp
T
T
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology*; D008297:Male; D010627:Phenethylamines / Q000494:pharmacology; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000187:drug effects*; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000187:drug effects*; D014191:Tranylcypromine / Q000494:pharmacology*
D000928:Antidepressive Agents; D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D001552:Benzazepines; D018491:Dopamine Agonists; D010627:Phenethylamines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D005473:Fluoxetine; D019257:Quinpirole; D014191:Tranylcypromine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C016868:N-n-propyl-N-phenylethyl-4(3-hydroxyphenyl)ethylamine hydrochloride; C067113:SK&F 81297; D001058:Apomorphine; D003891:Desipramine