Effect of noradrenergic system on the anxiolytic-like effect of DOI -5-HT2A and 2C agonists- in the four-plate test-

Authors
F. Massé, M. Hascoët, E. Dailly, M. Bourin.


Lab
Faculté de Médecine, Neurobiologie de l’anxiété et de la dépression, Nantes, France.

Journal
Psychopharmacology

Abstract
Rationale: 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 _-adrenergic ligands have also demonstrated an activity in other models of anxiety. A previous study demonstrated that the _2-adrenoceptor agonists abolished the anxiolytic-like effect of antidepressants.  Objectives: 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 _-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 _1-adrenoceptor agonist), prazosin 0.5 and 2 mg/kg (an _1-adrenoceptor antagonist) and idazoxan 1 and 4 mg/kg (an _2-adrenoceptor antagonist) did not modify the activity of DOI. Clonidine 0.06 mg/kg, guanabenz 0.125 and 0.5 mg/kg (two _2-adrenoceptor agonists) and guanfacine 0.06 and 0.125 mg/kg (a specific _2A-adrenoceptor agonist) completely abolished DOI-induced increase in punished passages. Conclusion: 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 _2-adrenoceptors.

BIOSEB Instruments Used:
Aron Test or Four Plates Test (LE830)

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