Influence of hippocampal GABAB receptor inhibition on memory in rats with acute β-amyloid toxicity

Abstract

The neurotransmitter γ-aminobutyric acid (GABA) is involved in the process of memory. It has been reported that the inhibition of GABAB receptors has beneficial effects on cognition. The aim of this study was to investigate the role of CGP35348 (a GABAB receptor antagonist) on dentate gyrus GABAB receptor inhibition and its effects on learning and memory impairments that had been induced in adult male rats by microinjection of β-amyloid (Aβ). Seventy Wistar male rats were randomly divided into seven groups: control, sham (receiving the Aβ vehicle only), Aβ, Aβ + CGP35348 (1, 10, and 100 μg/μL), and CGP35348 alone (10 μg/μL). Memory impairment was induced by unilateral interventricular microinjection of Aβ (6 μg/6 μL). Rats were cannulated bilaterally in the dentate gyrus, and then, they were treated for 20 consecutive days. Learning and memory were assessed using the novel object recognition and passive avoidance learning tests. The discrimination index and the step-through latency were significantly increased in the Aβ + CGP35348 group in comparison to the Aβ only group (P < 0.05 and P < 0.01, respectively). Data showed that the discrimination index was decreased in the Aβ + CGP35348 group in comparison with the control group (P < 0.05) and sham group (P < 0.01). Moreover, the step-through latency was significantly decreased in the Aβ + CGP35348 group in comparison to the control and sham groups (P < 0.01). Data from this study indicated that intra-hippocampal microinjection of the GABAB receptor antagonist counteracts the learning, memory, and cognitive impairments induced by Aβ. It can be concluded that the GABAB receptor antagonist is a possible therapeutic agent against the progression of acute Aβ toxicity-induced memory impairment.