Prolonged treatment with the specific 5-HT-uptake inhibitor citalopram: effect on dopaminergic and serotonergic functions.
The effect of prolonged administration of the clinically effective and specific serotonin (5-HT)-uptake-inhibitor, citalopram, has been studied in rats on behavioural measures of dopaminergic (DA) and serotonergic activity and on DA D-2, 5-HT2, alpha 1- and beta-adrenergic receptor number and affinity in vitro. Thirteen days treatment with citalopram in the diet (40 mg/kg/day) did not change receptor binding for either of the ligands studied, although citalopram was detected in high concentrations in brain and plasma and induced a 75% depletion of 5-HT in whole blood. This citalopram dose-regimen was followed by a potentiated hypermotility response to d-amphetamine. Also DA-dependent hypermotility induced by methylphenidate and (+)-3-PPP was increased. In contrast, the 5-HT2-receptor mediated head shake syndrome induced by 1-5-HTP or quipazine was decreased after prolonged citalopram treatment. Two weeks oral bolus treatment (10 mg/kg once or twice daily) with the 5-HT-uptake-inhibitors citalopram, fluoxetine, zimelidine, cyanimipramine or paroxetine induced d-amphetamine potentiation, whereas amitriptyline, nortriptyline, imipramine, iprindole, and mianserin treatment showed no effect. It is suggested that d-amphetamine potentiation induced by citalopram is mainly dependent on DA mechanisms, and that this profile is characteristic for preferential 5-HT-uptake-inhibitors. The lack of correlation between behavioural effect and receptor changes was important. Since citalopram has been shown to have clinical antidepressant activity, it is concluded that down-regulation of beta-adrenoceptors is not a prerequisite for antidepressant action.
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects; D015283:Citalopram; D003913:Dextroamphetamine / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011437:Propylamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D012701:Serotonin / Q000097:blood; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013997:Time Factors
D000928:Antidepressive Agents; D011437:Propylamines; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D015283:Citalopram; D012701:Serotonin; D003913:Dextroamphetamine