Evidence for the involvement of the monoaminergic system in the antidepressant-like action of two 4-amine derivatives of 10,11-dihydro-5H-dibenzo [a,d] cycloheptane in mice evaluated in the tail suspension test.
Our previous study described the synthesis of 4-amine derivatives of 10,11-dihydro-5H-dibenzo-alkylamine-cycloheptane, 4-amine (3-N,N-dimethylpropylamine)-10,11-dihydro-5H-dibenzo[a,d] cycloheptane-5-one (ADDCH1), and 1,2,3,4,8,9-hexahydro-dibenzocycloheptane[4,4a,5-ef]1,4-diazepin (ADDCH2), and the characterization of their antidepressant-like effect in the forced swimming test in mice. This study investigated the involvement of monoaminergic pathways in the antidepressant-like effect of these compounds in mice evaluated in the tail suspension test (TST), another animal model to screen antidepressant drugs. Our results show that the immobility time in the TST was significantly reduced by ADDCH1 (15 to 50 mg/kg, i.p.) or ADDCH2 (30 and 50 mg/kg, i.p.). The antidepressant-like effect of ADDCH1 (30 mg/kg, i.p.) in the TST was prevented by pre-treatment of mice with methysergide (2 mg/kg, i.p.), a non-selective serotonin receptor antagonist, p-chlorophenylalanine methylester (pCPA, 100 mg/kg, i.p.), an inhibitor of serotonin synthesis, prazosin (62.5 microg/kg, i.p.), an alpha1-adrenoceptor antagonist, or yohimbine (1 mg/kg, i.p.), an alpha2-adrenoceptor antagonist. In contrast, the antidepressant-like effect of ADDCH2 was antagonized only by yohimbine (1 mg/kg) or haloperidol (50 microg/kg, i.p.), a dopamine D2/D3/D4 receptor antagonist, and was not affected by methysergide, pCPA or prazosin. Altogether, the present results strongly suggest the differential involvement of monoaminergic systems, serotonin/noradrenaline (ADDCH1) and noradrenaline/dopamine (ADDCH2) pathways, respectively, in the antidepressant-like effect of dibenzosuberone compounds.
Duarte
Filipe Silveira
FS
Laboratory of Neuropharmacology, Department of Pharmacology, CCB, Universidade Federal de Santa Catarina, Florianópolis, SC, 88049-900, Brazil.
Lach
Gilliard
G
Martins
Paulo Roberto Codeço
PR
Romeiro
Gilberto Alves
GA
de Lima
Thereza Christina Monteiro
TC
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects*; D015306:Biogenic Monoamines / Q000494:pharmacology* / Q000502:physiology; D003508:Cycloheptanes / Q000494:pharmacology* / Q000627:therapeutic use; D003866:Depressive Disorder / Q000188:drug therapy*; D004195:Disease Models, Animal; D006220:Haloperidol; D019417:Hindlimb Suspension / Q000502:physiology*; D046353:Immobility Response, Tonic / Q000187:drug effects*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects
D000928:Antidepressive Agents; D015306:Biogenic Monoamines; D003508:Cycloheptanes; D006220:Haloperidol