Effect of noradrenergic system on the anxiolytic-like effect of DOI (5-HT2A/2C agonists) in the four-plate test.
BACKGROUND
Selective serotonin reuptake inhibitors and serotonin and noradrenaline reuptake inhibitors demonstrated an anxiolytic-like effect in the four-plate test (FPT). (+/-)-1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane (DOI; a 5-HT2A receptor agonist) also possessed strong anxiolytic-like effect in the same test. A 5-HT2A mechanism seems to be implicated in the mechanism of action of both antidepressants and DOI in this test. On the other hand, the alpha-adrenergic ligands have also demonstrated an activity in other models of anxiety. A previous study demonstrated that the alpha2-adrenoceptor agonists abolished the anxiolytic-like effect of antidepressants.


OBJECTIVE
The aim of the present study was to evaluate the role of noradrenergic system on the regulation of 5-HT2 receptors implicated in the DOI anxiolytic-like activity in the FPT.


METHODS
First, the effect of noradrenergic and serotonergic lesions on DOI anxiolytic-like activity was studied in the FPT. Second, the effect of co-administration of alpha-adrenoceptor ligands and DOI was evaluated in the same test.


RESULTS
The noradrenergic and serotonergic lesions had no effect on DOI (1 mg/kg) anti-punishment activity in the FPT. Adrafinil 0.25 and 4 mg/kg (an alpha1-adrenoceptor agonist), prazosin 0.5 and 2 mg/kg (an alpha1-adrenoceptor antagonist) and idazoxan 1 and 4 mg/kg (an alpha2-adrenoceptor antagonist) did not modify the activity of DOI. Clonidine 0.06 mg/kg, guanabenz 0.125 and 0.5 mg/kg (two alpha2-adrenoceptor agonists) and guanfacine 0.06 and 0.125 mg/kg (a specific alpha2A-adrenoceptor agonist) completely abolished DOI-induced increase in punished passages.


CONCLUSIONS
These results indicate that the DOI seems to act on the 5-HT2 receptors post-synaptically located. The effect of DOI is regulated by the alpha2-adrenoceptors.
Massé
Fabienne
F
EA 3256, Neurobiologie de l'anxiété et de la dépression, Faculté de Médecine, BP 53508, 1 rue Gaston Veil, 44035, Nantes cedex 01, France.
Hascoët
Martine
M
Dailly
Eric
E
Bourin
Michel
M
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D014151:Anti-Anxiety Agents; D001007:Anxiety / Q000523:psychology*; D001596:Benzylamines / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects; D003975:Diazepam / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D018757:GABA Modulators / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009498:Neurotoxins / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000662:Amphetamines; D014151:Anti-Anxiety Agents; D001596:Benzylamines; D018757:GABA Modulators; D009498:Neurotoxins; D017366:Serotonin Receptor Agonists; D012701:Serotonin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; C012102:DSP 4; D003975:Diazepam; D004298:Dopamine; D009638:Norepinephrine