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

Abstract

Rationale: 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) GABA(A) receptors on spatial and non-spatial novelty detection deficit, induced by a selective CB1 receptor agonist (ACPA), during a non-associative task.

Methods: Male mice weighing 30-35 g were used. Open field paradigm was employed to assess the spatial and non-spatial memory retention.

Results: Our data showed that intraperitoneal injection of the higher doses of ACPA (0.005, 0.01 and 0.02 mg/kg) decreases spatial change detection as well as the reaction to non-spatial novelty. Moreover, isolated intra-CA1 injection of bicuculline (GABA(A) receptor antagonist) at 0.0625, 0.125 and 0.25 μg/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 (GABA(A) receptor agonist) at 0.25, 0.5 and 1 μg/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 (0.02 mg/kg). Meanwhile, co-administration of the subthreshold and effective doses of muscimol and ACPA (0.005 mg/kg) could only impair the spatial change detection ability but not the reaction to non-spatial novelty.

Conclusion: Our results suggested that the ACPA induced impairment of memory retention, may occur through dorsal hippocampal (CA1) GABA(A) receptors thus, blockade of these receptors can possibly reverse this phenomenon.