Effect of chronic administration of antidepressant drugs on 5-HT2-mediated behavior in the rat following noradrenergic or serotonergic denervation

J Neural Transm Gen Sect. 1991;84(1-2):19-32. doi: 10.1007/BF01249106.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5,7-Dihydroxytryptamine / pharmacology
  • Animals
  • Antidepressive Agents / administration & dosage
  • Antidepressive Agents / pharmacology*
  • Behavior, Animal / drug effects*
  • Behavior, Animal / physiology
  • Benzylamines / toxicity
  • Brain Chemistry / drug effects
  • Denervation
  • Down-Regulation / drug effects
  • Infusions, Parenteral
  • Male
  • Norepinephrine / physiology*
  • Quipazine / toxicity
  • Rats
  • Rats, Inbred Strains
  • Receptors, Adrenergic, beta / drug effects
  • Receptors, Adrenergic, beta / physiology
  • Receptors, Serotonin / drug effects*
  • Receptors, Serotonin / physiology
  • Serotonin / physiology*


  • Antidepressive Agents
  • Benzylamines
  • Receptors, Adrenergic, beta
  • Receptors, Serotonin
  • 5,7-Dihydroxytryptamine
  • Serotonin
  • Quipazine
  • DSP 4
  • Norepinephrine