Reactivity of 5-HT1A receptor in adult rats after neonatal noradrenergic neurons' lesion--implications for antidepressant-like action.
The aim of this study was to assess the 5-HT1A receptor reactivity after neonatal noradrenergic neurons' lesion. DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine), 50 mg/kg, was administered 30 min after a selective serotonin reuptake inhibitor (SSRI)--zimelidine (10 mg/kg) on the 1st and 3rd day of life. Zimelidine was used to prevent serotonin (5-HT) depletion. 5-HT1A autoreceptor is involved in the regulation of 5-HT release as well as the pathogenesis of depression. During a microdialysis study of anaesthetized rats, the 5-HT1A receptor agonist, R-(+)-8-OH-DPAT (0.1 mg/kg), decreased 5-HT release in the medial prefrontal cortex of control rats but this effect was significantly attenuated in DSP-4-treated animals (10-12 weeks old). To further determine which type of receptor, either pre or postsynaptically located, is involved in the attenuated response to the 5-HT1A receptor agonist in lesioned rats, behavioral tests were conducted. In the forced swimming test, DSP-4 treated rats after saline injection, displayed shorter immobility time in comparison to control rats. R-(+)-8-OH-DPAT (0.5 mg/kg) evoked an antidepressant-like effect in control and DSP-4 treated rats in a learned helplessness paradigm as well as the forced swimming test. The results of this study provided further support for the exclusive desensitization of 5-HT1A autoreceptor in adult rats with neonatal lesion of the central noradrenergic system.
Dabrowska
Joanna
J
Department of Pharmacology, Medical University of Silesia, 38 Jordana St., 41-808 Zabrze, Poland. jdabrow@emory.edu
Nowak
Przemyslaw
P
Brus
Ryszard
R
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D018663:Adrenergic Agents / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D000928:Antidepressive Agents / Q000494:pharmacology; D001596:Benzylamines / Q000633:toxicity*; D003863:Depression / Q000188:drug therapy; D006380:Helplessness, Learned; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013997:Time Factors; D015031:Zimeldine / Q000494:pharmacology
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D018663:Adrenergic Agents; D000928:Antidepressive Agents; D001596:Benzylamines; D009638:Norepinephrine; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D015031:Zimeldine; C012102:DSP 4