Clonidine potentiates the effects of tranylcypromine, phenelzine and two analogues in the forced swimming test in mice.
OBJECTIVE
To compare tranylcypromine (TCP) and phenelzine (PLZ), two well-established inhibitors of monoamine oxidase (MAO), and 2 of their analogues, 4-fluorotranylcypromine (FTCP) and N2-acetylphenelzine (AcPLZ) respectively, with regard to effects in the forced swimming test, a behavioural test used to screen for potential antidepressant drugs.


METHODS
Mice were dropped individually into glass cylinders containing water. The duration of their immobility was scored during the last 4 minutes of the test.


RESULTS
Except for TCP at high doses, none of the drugs demonstrated activity when administered alone. All 4 drugs were active when given in combination with clonidine, an effect thought to be the result of mixed action at 5-HT1A and 5-HT2 receptors and the noradrenergic system. 5-HT18 receptors do not seem to be implicated, as lithium did not potentiate the effect of any of the drugs. Quinine activation of AcPLZ suggests that this analogue acts on 5-HT3 receptors.


CONCLUSIONS
FTCP and AcPLZ demonstrated anti-immobility activity in the forced swimming test when used in association clonidine. These findings confirm previous neurochemical findings suggesting that these drugs have antidepressant properties.
Bourin
Michel
M
Neurochemical Research Unit, Department of Psychiatry, University of Alberta, Edmonton, Alta. mbourin@sante.univ-nantes.fr
Hascoët
Martine
M
Colombel
Marie Claude
MC
Coutts
Ronald T
RT
Baker
Glen B
GB
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D003000:Clonidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D008094:Lithium / Q000494:pharmacology; D008297:Male; D051379:Mice; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010624:Phenelzine / Q000494:pharmacology*; D011803:Quinine / Q000494:pharmacology; D013550:Swimming / Q000523:psychology; D014191:Tranylcypromine / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D000928:Antidepressive Agents; D008996:Monoamine Oxidase Inhibitors; D014191:Tranylcypromine; D008094:Lithium; D011803:Quinine; D003000:Clonidine; D010624:Phenelzine