Effect of 5-HT1A agonists on stress-induced deficit in open field locomotor activity of rats: evidence that this model identifies anxiolytic-like activity.
Deficits in locomotion and exploratory behaviour in an open field were induced in rats by restraint for 2 hr, 23 hr before testing. Diazepam, 0.62 and 1.25 mg/kg, intraperitoneally (i.p.), 15 min before testing, reversed the stress-induced reduction in locomotion; 1.25 mg/kg also attenuated the effect of stress on exploration (rearing and object exploring). Diazepam did not affect the activity of controls. A putative anxiogenic compound, pyrazoloquinoline (CGS 8216, 10 mg/kg administered 30 min before testing), also markedly reduced locomotion and exploration and the effect was reversed by 2.5 mg/kg diazepam, 15 min before testing. Buspirone, 0.1 mg/kg subcutaneously (s.c.) 15 min before testing, significantly attenuated the effect of stress on locomotion and exploration but had no effect in controls. Larger doses (0.5 and 1.0 mg/kg) markedly reduced the behavioural measures in controls and did not modify or enhance the effect of stress. 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), 0.25 and 0.5 mg/kg (s.c.), 1 hr before testing, significantly attenuated the reduction in locomotion without affecting rearing and object-exploring in stressed rats. At doses from 0.125 to 0.5 mg/kg, 8-OH-DPAT reduced exploration in control rats. Two hr after restraint (corresponding to 21 hr before testing in the open field) 8-OH-DPAT, 0.125 to 2 mg/kg (s.c.), did not modify the open field deficits, caused by stress. In these treatment conditions, 0.5 and 2 mg/kg 8-OH-DPAT reduced locomotion and exploration in control rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Carli
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M
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Prontera
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Samanin
R
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D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D002065:Buspirone / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D003975:Diazepam / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D008954:Models, Biological; D009043:Motor Activity / Q000187:drug effects*; D011720:Pyrazoles / Q000037:antagonists & inhibitors; D051381:Rats; D011985:Receptors, Serotonin / Q000502:physiology*; D013315:Stress, Psychological / Q000523:psychology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D011720:Pyrazoles; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; C033830:2-phenylpyrazolo(4,3-c)quinolin-3(5H)-one; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D003975:Diazepam; D003891:Desipramine; D002065:Buspirone