title: On the role of noradrenergic neurotransmission in the action of desipramine and amitriptyline in animal models of depression.
abstract: Three weeks of treatment with desipramine (DMI) and amitriptyline (AMI) reduced the hypothermic action of clonidine in rats. Both electrolytic and 6-hydroxydopamine lesions of the locus coeruleus (LC) and administration of DSP-4 counteracted the reduction of clonidine hypothermia produced by antidepressants. Lesions of the LC and DSP-4 administration also antagonized the anti-immobility action of single doses of DMI but failed to modulate the action of AMI in the forced swim test. Chronic DMI action on the rat immobility was reduced by 6-hydroxydopamine lesions of the LC: other lesions (electrolytic, DSP-4) were ineffective. Electrical stimulation of the LC increased the rat activity in the forced swim paradigm, producing an effect similar to that of antidepressants. The anti-immobility effect of DMI as well as LC stimulation were antagonized by drugs blocking alpha-adrenoceptors (phenoxybenzamine, prazosin) but not by propranolol, a non-selective antagonist of beta-adrenoceptors. On the other hand, the anti-immobility action of AMI was unchanged by all adrenolytics used in that study. The results indicate that the LC system and alpha 1-adrenoceptors play an important role in the antidepressive action of DMI, but not AMI, in the forced swim test.
mesh_terms: D000639:Amitriptyline / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents; D001596:Benzylamines / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology*; D006892:Hydroxydopamines / Q000494:pharmacology; D008125:Locus Coeruleus / Q000187:drug effects; D008297:Male; D009638:Norepinephrine / Q000502:physiology*; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D013564:Sympathetic Nervous System / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D000928:Antidepressive Agents; D001596:Benzylamines; D006892:Hydroxydopamines; D000639:Amitriptyline; D016627:Oxidopamine; D003000:Clonidine; C012102:DSP 4; D003891:Desipramine; D009638:Norepinephrine