Role of serotonergic input in the down-regulation of beta-adrenoceptors following long-term clorgyline treatment.
Administration of the selective monoamine oxidase (MAO) type A-inhibiting antidepressant clorgyline (1 mg/kg per day) to rats for 21 days caused a significant decrease in cortical [3H]dihydroalprenolol binding. Selective lesioning of central serotonergic axons by 5,7-dihydroxytryptamine (5,7-DHT; confirmed by the presence of the serotonin syndrome in response to a 40 mg/kg dose of 5-hydroxytryptophan (5-HTP) or inhibition of 5-HT synthesis by parachlorophenylalanine (PCPA) caused significant 5-HT and 5-HIAA depletions in the cortex without much effect on NE and DA concentrations, but did not have any significant effect on beta-adrenoceptor density, and furthermore failed to attenuate clorgyline-induced decreases in beta-adrenoceptor density. Clorgyline treatment partially antagonized 5-HT depletion by the 5,7-DHT lesion or PCPA treatment. These findings suggest that due to their ability to raise 5-HT concentrations, MAO-inhibiting antidepressants may be a better alternative than the tricyclics in treating depressed patients with reduced 5-HT if down-regulation of beta-adrenoceptors is critical for antidepressant efficacy.
Aulakh
C S
CS
Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, MD 20892.
Cohen
R M
RM
Dauphin
M M
MM
McLellan
C A
CA
Murphy
D L
DL
D015116:5,7-Dihydroxytryptamine / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D003010:Clorgyline / Q000494:pharmacology*; D004102:Dihydroxytryptamines / Q000633:toxicity*; D004298:Dopamine / Q000032:analysis; D010134:Fenclonine / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000032:analysis; D007276:Injections, Intraventricular; D008297:Male; D009638:Norepinephrine / Q000032:analysis; D011437:Propylamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D012701:Serotonin / Q000502:physiology*; D013997:Time Factors
D004102:Dihydroxytryptamines; D011437:Propylamines; D011943:Receptors, Adrenergic, beta; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D003010:Clorgyline; D010134:Fenclonine; D004298:Dopamine; D009638:Norepinephrine