Involvement of the CA1 GABAA receptors in ACPA-induced impairment of spatial and non-spatial novelty detection in mice

• Published in: Neurobiology of learning and memory 2013-02, Vol.100, p.32-40
• Main Authors: Yousefi, Behnam, Farjad, Meisam, Nasehi, Mohammad, Zarrindast, Mohammad Reza
• Format: Article
• Language: English
• Subjects: ACPA; Animal memory; Animals; Arachidonic Acids - pharmacology; Behavior, Animal - drug effects; Behavior, Animal - physiology; Behavioral psychophysiology; Bicuculline; Bicuculline - pharmacology; Biological and medical sciences; CA1 Region, Hippocampal - drug effects; CA1 Region, Hippocampal - metabolism; Cannabinoid CB1 receptors; Data processing; Fundamental and applied biological sciences. Psychology; GABA-A Receptor Agonists - pharmacology; GABA-A Receptor Antagonists - pharmacology; gamma -Aminobutyric acid A receptors; Glutamatergic transmission; Hippocampus; Hippocampus (CA1); Male; Memory; Memory - drug effects; Memory - physiology; Mice; Muscimol; Muscimol - pharmacology; Nervous system; Neurobiology; Neurotransmitters; Novelty; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Receptors, GABA-A - metabolism; Rodents; Spatial and non-spatial memory; Spatial Behavior - drug effects; Spatial Behavior - physiology
• ISSN: 1074-7427; 1095-9564
• DOI: 10.1016/j.nlm.2012.12.001

► ACPA decreases spatial change detection and reaction to non-spatial novelty. ► Bicuculline (intra-CA1) did not alter spatial and non-spatial memory. ► Muscimol (intra-CA1) impaired spatial and non-spatial memory. ► Bicuculline restored ACPA-induced spatial and non-spatial memory deficit. ► Muscimol only potentiated spatial memory deficit by ACPA but not non-spatial memory. Cannabinoids are shown to modulate the hippocampal memory processing through different neuronal systems such as GABAergic and glutamatergic. This study investigates the effects of dorsal hippocampal (CA1) GABAA receptors on spatial and non-spatial novelty detection deficit, induced by a selective CB1 receptor agonist (ACPA), during a non-associative task. Male mice weighing 30–35g were used. Open field paradigm was employed to assess the spatial and non-spatial memory retention. Our data showed that intraperitoneal injection of the higher doses of ACPA (0.005, 0.01 and 0.02mg/kg) decreases spatial change detection as well as the reaction to non-spatial novelty. Moreover, isolated intra-CA1 injection of bicuculline (GABAA receptor antagonist) at 0.0625, 0.125 and 0.25μg/mouse did not alter the spatial change detection and non-spatial novelty in saline treated mice. On the other hand, intra-CA1 injection of the higher doses of muscimol (GABAA receptor agonist) at 0.25, 0.5 and 1μg/mouse, not only impaired the spatial change detection on its own, but also affected the reaction to non-spatial novelty. In addition, the subthreshold dose of bicuculline reversed the impaired spatial and non-spatial memory in mice which received post-training injection of ACPA effective dose (0.02mg/kg). Meanwhile, co-administration of the subthreshold and effective doses of muscimol and ACPA (0.005mg/kg) could only impair the spatial change detection ability but not the reaction to non-spatial novelty. Our results suggested that the ACPA induced impairment of memory retention, may occur through dorsal hippocampal (CA1) GABAA receptors thus, blockade of these receptors can possibly reverse this phenomenon.