Dopaminergic system in CA1 modulates MK-801 induced anxiolytic-like responses

• Published in: Pharmacology, biochemistry and behavior Vol. 103; no. 1; pp. 102 - 110
• Main Authors: Zarrindast, Mohammad Reza, Nasehi, Mohammad, Pournaghshband, Mahnaz, Ghorbani Yekta, Batool
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2012
• Subjects: Animals; Anxiety - chemically induced; Anxiety - physiopathology; Anxiolytic-like response; Benzazepines - pharmacology; CA1 Region, Hippocampal - drug effects; CA1 Region, Hippocampal - physiology; Dizocilpine Maleate - pharmacology; Dopamine - physiology; Dopamine D2 Receptor Antagonists; Dorsal hippocampus (CA1); Elevated plus-maze; Excitatory Amino Acid Antagonists - pharmacology; Male; Maze Learning; MK801; Rat(s); Rats; Rats, Wistar; Receptors, Dopamine D1 - antagonists & inhibitors; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; SCH23390; Sulpiride; Sulpiride - pharmacology; Rat(s); Anxiolytic-like response; SCH23390; MK801; Elevated plus-maze; Sulpiride; Dorsal hippocampus (CA1)
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2012.07.016

Today, there is relatively no debate on the notion that NMDA receptor antagonist agents in the hippocampus induce anxiolytic-like effects through distinct mechanisms. There is also a bulk of studies showing the involvement of the dopaminergic system in NMDA induced behaviors. Thus, on the basis of the involvement of dopaminergic system in anxiety-related behaviors, the present study aimed to investigate the involvement of the dorsal hippocampal (CA1) dopaminergic system in anxiolytic-like responses induced by MK801 (NMDA receptor antagonist) in male Wistar rats. We used the elevated plus maze to test anxiety. This apparatus has widely been employed to test parameters of anxiety-related behaviors including the open arm time percentage (%OAT), open arm entries percentage (%OAE), locomotor activity, grooming (the rat rubs its face), rearing (the rat maintains an erect posture) and defecation (the number of boli defection). The data showed that, intra-CA1 injection of MK801 (2μg/rat) increases %OAT and %OAE but not other exploratory behaviors, indicating an anxiolytic-like effect. Moreover, sole intra-CA1 injection of SCH23390, dopamine D1 receptor antagonist, (0.25, 0.5 and 1μg/rat) and sulpiride, dopamine D2 receptor antagonist, (0.25, 0.5 and 0.75μg/rat) did not alter anxiety-like behaviors. Co-administration of subthreshold doses of SCH23390 (0.5μg/rat) and MK801 (0.5g/rat), induced anxiolytic-like behaviors. Furthermore, intra-CA1 administration of different doses of sulpiride (0.12, 0.5 and 0.75μg/rat), 5min before the injection of an effective dose of MK801 (2μg/rat), decreased %OAT and %OAE, however did not alter other exploratory behaviors induced by MK801. Our results suggested a modulatory effect of the CA1 dopaminergic system on the anxiolytic-like effects induced by MK801. ► Intra-CA1 injection of MK801 induced anxiolytic-like behaviors. ► Intra-CA1 injection of SCH23390 and sulpiride induced anxiolytic-like behaviors. ► Intra-CA1 co-injection of SCH23390 increased anxiolytic-like behaviors by MK801. ► Intra-CA1 co-administration of sulpiride block anxiolytic-like behaviors by MK801.