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  • 5-HT1A receptor agonists  (1)
  • 5-HT1A receptor antagonist  (1)
  • 1
    ISSN: 1432-2072
    Keywords: Stretched approach posture ; Ambivalent behaviour ; Intention movements ; Ethological observation ; Rat ; Anxiety disorders ; Benzodiazepines ; 5-HT1A receptor agonists ; 5-HT uptake inhibitors ; Clonidine ; Clorgyline ; Anxiogenic drugs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of various psychotropic drugs on the ambivalent behaviour “stretched approach posture” (SAP) in the rat was assessed. SAP was elicited after a mild startle reaction due to physical contact with an electrified prod at one end of a straight runway. Using ethological observation methods, SAP as well as intention movements, prod contact, crossings, rearing, exploration, grooming and immobility were recorded. The benzodiazepine receptor agonists chlordiazepoxide, diazepam and alprazolam, the 5-HT1A receptor agonists flesinoxan and ipsapirone and the 5-HT uptake inhibitor clomipramine selectively (no effect on crossings) reduced SAP. Except for alprazolam, these drugs also reduced intention movements. In addition, chlordiazepoxide and diazepam enhanced prod contact. Reductions of SAP and intentions with concomitant reductions of crossings (nonspecific anti-ambivalent effects) were established for the α2-adrenoceptor agonist clonidine and the MAO inhibitor clorgyline. The 5-HT uptake inhibitor fluvoxamine suppressed intention movements, but not SAP. The mixed 5-HT/NA uptake inhibitor imipramine did not significantly affect SAP or intentions, but reduced crossings. The 5-HT2C/1B receptor agonist m-CPP, the inverse BZD receptor agonists FG 7142 and DMCM, and the α2-adrenoceptor antagonist yohimbine, to all of which putative anxiogenic effects have been ascribed, had no effect on SAP directed towards the prod. m-CPP, however, produced an increase in the stretched posture directed away from the prod (SAwayP). FG 7142 reduced intentions while strongly enhancing immobility (freezing). SAwayP and/or freezing may possibly reflect anxiogenic properties of drugs. The putative anxiogenic drug pentylenetetrazol false positively reduced SAP while increasing exploration. The dopamine-D2 receptor antagonist haloperidol and the catecholamine releaserdl-amphetamine had no effect on ambivalent behaviour. The muscarine receptor antagonist scopolamine reduced SAP and intentions while stimulating crossings. Finally, the 5-HT2C receptor antagonist ritanserine, the CCKA receptor antagonist devazepide, the CCKB receptor antagonist L-365.260 and the strychnine-insensitive glycine site antagonist 7-Cl-kynurenic acid were without effect on the behaviours in this paradigm using single doses. In conclusion, SAP and intention movements were reduced selectively by anxiolytic agents from different classes, including benzodiazepine receptor agonists, 5-HT1A receptor agonists and a 5-HT uptake inhibitor, whereas an α2-adrenoceptor agonist and a MAO inhibitor reduced SAP non-selectively. SAP in relation to other behaviours may therefore serve as a valuable paradigm to characterize anxiolytic drugs.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2072
    Keywords: Key words Anxiety ; Fear-potentiated startle response ; 8-OH-DPAT ; Flesinoxan ; WAY 100 ; 635 ; (±)-Pindolol ; DU 125 ; 530 ; Lower lip retraction ; 5-HT1A receptor agonist ; 5-HT1A receptor antagonist ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The present study investigated whether the anxiolytic effect of 5-HT1A receptor agonists on the fear-potentiated startle response could be antagonized by 5-HT1A receptor antagonists. Therefore, control and fear-potentiated startle amplitudes were measured after co-administration of vehicle, flesinoxan (10 mg/kg PO) or 8-OH-DPAT (0.3 mg/kg SC) and DU 125,530 (0, 1, 3 and 10 mg/kg SC), (±)-pindolol (0, 3, 10 and 30 mg/kg SC) or WAY 100,635 (0, 0.1, 0.3 and 1 mg/kg SC). Unexpectedly, the three antagonists themselves as measured in the vehicle-pretreatment groups dose-dependently decreased startle potentiation. Further, DU 125,530 and WAY 100,635 were able to reverse the attenuating effect of 8-OH-DPAT, while no antagonism of the flesinoxan effect on startle potentiation was found. In contrast, both the flesinoxan- and 8-OH-DPAT-induced lower lip retraction were antagonized by DU 125,530 and WAY 100,635, but not by (±)-pindolol. The findings of the present study suggest that drugs acting on 5-HT1A receptors differentially affect lower lip retraction and startle potentiation probably mediated by different neuronal populations.
    Type of Medium: Electronic Resource
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