Determination of the role of noradrenergic and 5-hydroxytryptaminergic neurones in postsynaptic alpha 2-adrenoceptor desensitization by desipramine and ECS.
1. Experiments were conducted to determine the respective roles which noradrenergic and 5-hydroxytryptaminergic neurones play in the down-regulation of postsynaptic alpha 2-adrenoceptors by desipramine and electroconvulsive shock (ECS). The functional status of these receptors was monitored by use of clonidine-induced mydriasis in conscious mice. 2. Mydriasis to clonidine (0.1 mg kg-1, i.p.) was markedly attenuated by administration of either desipramine (10 mg kg-1, i.p.) for 14 days or ECS (200 V, 2s) given five times over ten days confirming our previous observations. 3. The neurotoxin, DSP-4 (100 mg kg-1, i.p. X 2), reduced brain noradrenaline levels by 64% and abolished the mydriasis induced by the noradrenaline releasing agent and reuptake inhibitor, methamphetamine, without significantly altering the response to clonidine, confirming our earlier results. This lesion prevented the attenuation of clonidine mydriasis by repeated administration of desipramine, but not ECS. 4. Lesioning of central 5-hydroxytryptaminergic neurones with 5,7-dihydroxytryptamine (75 micrograms, i.c.v.) had no influence on the reduction in clonidine mydriasis produced by repeated administration of either desipramine or ECS. 5. Since noradrenergic neurones are essential for the desensitization of postsynaptic alpha 2-adrenoceptors by desipramine, it indicates that this effect is probably the result of increased synaptic noradrenaline levels. This mechanism is not responsible for the change induced by ECS because this adaptation is independent of an intact noradrenergic input. 5-HT-containing neurones do not play a permissive role in the down-regulation of postsynaptic alpha 2-adrenoceptors by either antidepressant treatment.
Heal
D J
DJ
Boots Pharmaceuticals Research Department, Nottingham.
Prow
M R
MR
Buckett
W R
WR
D000818:Animals; D015306:Biogenic Monoamines / Q000032:analysis; D001923:Brain Chemistry; D003000:Clonidine / Q000494:pharmacology; D003891:Desipramine / Q000008:administration & dosage / Q000494:pharmacology*; D015536:Down-Regulation; D004597:Electroshock; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009474:Neurons / Q000502:physiology; D009638:Norepinephrine / Q000032:analysis; D011680:Pupil / Q000187:drug effects; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000032:analysis
D015306:Biogenic Monoamines; D011942:Receptors, Adrenergic, alpha; D012701:Serotonin; D003000:Clonidine; D003891:Desipramine; D009638:Norepinephrine