Effects of antidepressant drugs, selective noradrenaline-or 5-hydroxytryptamine uptake inhibitors, on apomorphine-induced hypothermia in mice.
Antidepressant drugs which are selective noradrenaline (NA) uptake inhibitors (desipramine, maprotiline, oxaprotiline, talsupram: 0.625-10 mg/kg) antagonized dose-dependently hypothermia induced by 16 mg/kg apomorphine (APO) in mice. Of the two stereoisomers of oxaprotiline, only that inhibiting NA uptake was active. Antidepressants which are selective 5-hydroxytryptamine (5-HT) uptake inhibitors (citalopram, fluvoxamine: 2.5-40 mg/kg) did not affect APO (16 mg/kg)-induced hypothermia. Neither NA nor 5-HT uptake inhibitors counteracted hypothermia induced by 1 mg/kg APO, a dose which is easily antagonized by low doses of dopamine receptor blockers. The antagonistic action of desipramine towards APO (16 mg/kg)-induced hypothermia was prevented by phenoxybenzamine, prazosin and (-)-propranolol, while (+)-propranolol and cyproheptadine were inactive. St. 587 (an alpha 1-adrenoceptor agonist) or salbutamol (an agonist of beta-adrenoceptors) attenuated APO (16 mg/kg)-induced hypothermia: given jointly, the drugs completely reversed it. m-CPP, a 5-HT receptor agonist, did not affect APO (16 mg/kg)-induced hypothermia. In conclusion, the antagonistic action of antidepressant drugs towards APO (16 mg/kg)-induced hypothermia in mice did not reflect their "antidepressant properties", dopamine antagonism or their action on 5-HT receptors, only their effects on the NA uptake and/or NA transmission. Both alpha 1 and beta-adrenoceptors are involved in this antagonistic action.
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000037:antagonists & inhibitors*; D001831:Body Temperature / Q000187:drug effects*; D001921:Brain / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical; D008297:Male; D051379:Mice; D009638:Norepinephrine / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects
D000928:Antidepressive Agents; D012701:Serotonin; D001058:Apomorphine; D009638:Norepinephrine