Behavioural evidence for simultaneous dual changes of 5-HT receptor subtypes: mode of antidepressant action?
Effects of the classic antidepressant imipramine and of an imipramine-like potential antidepressant dihydroergosine were studied in mice, rats and guinea pigs using behavioural models associated with the activation of 5-HT2 and 5-HT1 receptors respectively. Both drugs given in a single dose inhibited the 5-HT2 mediated behaviour for 24 and 48 h respectively and simultaneously stimulated 5-HT1 mediated behaviour for 6 days. Blockade of 5-HT2 receptors could have reduced their inhibitory influence on 5-HT1 receptors. We propose that the interplay between the two receptor subtypes controls the serotoninergic transmission. This idea throws a new light on the mode of action of antidepressants.
Pericić
D
D
Department of Experimental Biology and Medicine, Rudjer Bosković Institute, Zagreb, Yugoslavia.
Manev
H
H
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004879:Ergotamines / Q000494:pharmacology; D006168:Guinea Pigs; D006257:Head; D007099:Imipramine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009207:Myoclonus; D010293:Pargyline / Q000494:pharmacology; D051381:Rats; D011985:Receptors, Serotonin / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*; D013577:Syndrome
D004879:Ergotamines; D011985:Receptors, Serotonin; D012701:Serotonin; C037580:9,10-dihydroergosine; D010293:Pargyline; D007099:Imipramine