Serotonergic mechanisms involved in the exploratory behaviour of mice in a fully automated two-compartment black and white text box.
A fully automated version of the black and white two-compartment box for mice is presented. The anxiolytic-like effects of the benzodiazepines, diazepam and chlordiazepoxide, were confirmed, and the involvement of serotonergic mechanisms was studied in this animal model of anxiety. The partial 5-HT1A receptor agonists, buspirone and ipsapirone showed anxiolytic-like effects in a limited dose interval. The full agonist hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT) was inactive. The non-selective 5-HT1 receptor agonist, eltoprazine, induced marked increases of exploratory behaviour in the white compartment over a broad range of doses. Also pindolol a mixed 5-HT1A/1B and beta-adrenergic receptor antagonist showed anxiolytic-like effects, whereas another compound with a similar profile (-)-, penbutolol and the beta-adrenoceptor antagonist ICI 118,551, was inactive. The 5-HT2A/2C receptor antagonist, ritanserin, showed anxiogenic-like, and the 5-HT3 receptor antagonists, zacopride and ondansetron, showed anixiolytic-like effects. An overall increase of serotonergic activity by means of 5-HT uptake inhibition (citalopram), 5-HT release (fenfluramine) or administration of a 5-HT precursor (1-5-HTP) facilitated exploratory activity in the white compartment. Reduction of serotonergic activity by treatment with the 5-HT depletor p-chloro-phenylalanine methyl ester (PCPA) did not change the exploratory behaviour, but attenuated the response to fenfluramine significantly.
H. Lundbeck A/S, Copenhagen-Valby, Denmark.
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D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001008:Anxiety Disorders / Q000188:drug therapy / Q000209:etiology; D002065:Buspirone / Q000494:pharmacology; D002707:Chlordiazepoxide / Q000494:pharmacology; D003624:Darkness; D003975:Diazepam / Q000494:pharmacology; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects*; D005277:Fenfluramine / Q000494:pharmacology; D008027:Light; D008297:Male; D051379:Mice; D010394:Penbutolol / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000319:Adrenergic beta-Antagonists; D014151:Anti-Anxiety Agents; D002065:Buspirone; D002707:Chlordiazepoxide; D003975:Diazepam; D005277:Fenfluramine; D010394:Penbutolol; D011412:Propanolamines; D011743:Pyrimidines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; C026777:ICI 118551; C043077:ipsapirone