Participation of GABAA receptors in the modulation of experimental anxiety by tachykinin agonists and antagonists in mice.
Mice were acutely intraperitoneally treated with diazepam (DZP), pentylenetetrazol (PTZ) or NaCl 0.9% (control group), and 15 min later, the DZP-treated group received substance P (SP), neurokinin A (NKA; NK1 and NK2 natural preferential agonists), [Trp7 beta-Ala8] NKA(4-10) (Trp-7; NK3 antagonist) or vehicle intracerebroventricularly, whereas the PTZ-treated group was intracerebroventricularly administered with FK 888, SR 48968 (NK1 and NK2 antagonists, respectively) or senktide (SENK--[succinil-Asp6, MePhe8] substance P(6-11); NK3 agonist), or vehicle immediately before they were submitted to the elevated plus-maze (EPM) test. Another group of animals was repeatedly treated with increasing doses of DZP or NaCl 0.9% intraperitoneally for 28 days, and 3 days after the last injection (test day), animals received DZP, FK 888, SR 48968, SENK or vehicle intracerebroventricularly, or DZP (NaCl 0.9%) intraperitoneally before the EPM evaluation. The anxiolytic action of the acute treatment with DZP was inhibited by the central administration of NKA and Trp-7 but not by SP. NK1 and NK2 antagonists, but not NK3 agonist, blocked the anxiogenic action of PTZ, as evaluated in the plus-maze test. Flumazenil (FLM), a benzodiazepine antagonist, was not able to inhibit the anxiolytic profile of action induced by the NK2 antagonist. Central administration of FK 888 and SR 48968 promoted anxiolytic effects in both control and DZP-withdrawn animals, suggesting a clear relationship between the GABAergic and the tachykinergic systems, mostly involving NK1 and NK2 receptors, in the modulation of experimental anxiety in mice.
D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000378:metabolism*; D003975:Diazepam / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D051379:Mice; D011963:Receptors, GABA-A / Q000502:physiology*; D018039:Receptors, Tachykinin / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000502:physiology; D015320:Tachykinins / Q000502:physiology
D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D018039:Receptors, Tachykinin; D015320:Tachykinins; D003975:Diazepam