Involvement of the CA1 GABAA receptors in MK-801-induced anxiolytic-like effects: an isobologram analysis.
There seems to be a close relationship between hippocampal N-methyl-D-aspartic acid (NMDA) and GABAA receptors with respect to the modulation of behavior that occurs in the CA1 region of the hippocampus. This study investigated the possible involvement of the CA1 GABAA receptors in anxiolytic-like effects induced by (+)-MK-801 (a noncompetitive antagonist of the NMDA subtype of the glutamate receptor). Male Wistar rats were subjected to the elevated plus-maze apparatus and open arm time (%OAT), and open arm entries (%OAE) for anxiety-related behaviors, and closed arm entries that correspond to the locomotor activity were assessed. An intra-CA1 injection of (+)-MK-801 (2 μg/rat) and muscimol (0.5 μg/rat; a GABAA receptor agonist) increased %OAT and %OAE by themselves while not altering the closed arm entries, indicating an anxiolytic-like effect of these drugs. Injection of bicuculline (0.1, 0.25, and 0.5 μg/rat; a GABAA receptor antagonist) did not alter any of the anxiety-related parameters. An intra-CA1 injection of a subthreshold dose of muscimol (0.1 μg/rat) or bicuculline (0.5 μg/rat), 5 min before injection of subthreshold and effective doses of (+)-MK-801 (0.5, 1 and 2 μg/rat), increased and decreased the anxiolytic-like effect of (+)-MK-801, respectively. The isobologram analysis of these findings suggested a synergistic anxiety-like effect of intra-CA1 (+)-MK-801 and muscimol. In conclusion, the CA1 GABAA receptors appear to be involved in anxiolytic-like behaviors induced by (+)-MK-801.
aAlborz University of Medical Sciences, Karaj bDepartment of Cardiovascular Surgery, Baqiyatallah University of Medical Sciences cDepartment of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran dDepartment of Biology, Faculty of Basic Sciences, Garmsar Branch, Islamic Azad University, Garmsar eDepartment of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.
Mohammad-Hasan
MH
Naseri
Saeed
S
Hesami-Tackallou
Mohammad
M
Torabi-Nami
Mohammad-Reza
MR
Zarrindast
Mohammad
M
Nasehi
D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy* / Q000473:pathology*; D001640:Bicuculline / Q000494:pharmacology; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D018682:GABA Agents / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008845:Microinjections; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*
D014151:Anti-Anxiety Agents; D018682:GABA Agents; D011963:Receptors, GABA-A; D009118:Muscimol; D016291:Dizocilpine Maleate; D001640:Bicuculline