Effect of milnacipran and desipramine on noradrenergic alpha 2-autoreceptor sensitivity.
1. The effects of chronic administration with milnacipran and desipramine on the noradrenergic alpha 2-autoreceptor sensitivity in the rat hypothalamus were compared. 2. Rats were administered, in their diet, milnacipran (50 mg/kg/day for 21 days, 24 h wash-out), desipramine (35 mg/kg/day for 21 days, 24 h wash out) or desipramine (14 mg/kg/day for 21 days, 41 h wash-out). Hypothalamic slices were incubated with [3H]noradrenaline, superfused and stimulated electrically. 3. Chronic administration with milnacipran did not modify basal or electrically induced release of [3H]noradrenaline, tissue incorporation of [3H]noradrenaline or the sensitivity of the alpha 2-autoreceptor assessed by the inhibition of the stimulation-evoked release of [3H]noradrenaline by the alpha 2-adrenoceptor agonist, guanabenz, in comparison to controls. After chronic desipramine (35 mg/kg), basal and evoked release of [3H]noradrenaline were increased, tissue incorporation of [3H]noradrenaline decreased and the inhibitory effect of guanabenz was diminished. At the lower dose (14 mg/kg), chronic desipramine increased only the evoked release of noradrenaline but did not modify the sensitivity of the alpha 2-autoreceptor. 4. Desipramine at 35 mg/kg remains in the tissue after 24 h wash out, causing a reduction of uptake and complicating the interpretation of the data.
Moret
C
C
Neurobiology Division I, Centre de Recherche Pierre Fabre Castres, France.
Briley
M
M
D000818:Animals; D000928:Antidepressive Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003521:Cyclopropanes / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003891:Desipramine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004558:Electric Stimulation; D006143:Guanabenz / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008297:Male; D000078764:Milnacipran; D009638:Norepinephrine / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism
D000928:Antidepressive Agents; D003521:Cyclopropanes; D018341:Receptors, Adrenergic, alpha-2; D012701:Serotonin; D000078764:Milnacipran; D006143:Guanabenz; D003891:Desipramine; D009638:Norepinephrine