Effect of chronic administration of antidepressant drugs on 5-HT2-mediated behavior in the rat following noradrenergic or serotonergic denervation.
Chronic (14 day) administration of several pharmacologically-distinct antidepressant drugs resulted in marked reductions in the serotonin2 (5-HT2)-mediated quipazine-induced head shake response which were accompanied by significant reductions in the density of cortical beta-adrenergic and 5-HT2 binding sites. Noradrenergic (DSP4[N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine]-induced) and serotonergic (5,7-DHT[5,7-dihydroxytryptamine]-induced) lesions either attenuated or blocked antidepressant-induced reductions in 5-HT2-mediated behavior. DSP4- and 5,7-DHT lesions did not alter the down-regulation of 5-HT2 binding sites produced by imipramine, desipramine, phenelzine or iprindole. To a large extent, the antagonism of antidepressant-induced reductions in 5-HT2-mediated behavior was coincident with the blockade of down-regulation of beta-adrenergic binding sites by both noradrenergic and serotonergic denervation. The functional interrelationship of 5-HT2 and beta-adrenergic receptors suggested by the present findings may provide insight into a common mechanism underlying the action of pharmacologically-distinct antidepressant drugs.
Eison
A S
AS
CNS Research, Bristol-Myers Squibb Company, Wallingford, CT.
Yocca
F D
FD
Gianutsos
G
G
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D001596:Benzylamines / Q000633:toxicity; D001923:Brain Chemistry / Q000187:drug effects; D003714:Denervation; D015536:Down-Regulation / Q000187:drug effects; D007263:Infusions, Parenteral; D008297:Male; D009638:Norepinephrine / Q000502:physiology*; D011814:Quipazine / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D012701:Serotonin / Q000502:physiology*
D000928:Antidepressive Agents; D001596:Benzylamines; D011943:Receptors, Adrenergic, beta; D011985:Receptors, Serotonin; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D011814:Quipazine; C012102:DSP 4; D009638:Norepinephrine