Gaba-Cannabinoid Interplays in the Dorsal Hippocampus and Basolateral Amygdala Mediate Morphine-Induced Amnesia Publisher Pubmed



Sharifi KA¹ ; Rezayof A² ; Alijanpour S³ ; Zarrindast MR^{4, 5, 6, 7} Show Affiliations
Source: Brain Research Bulletin Published:2020

Abstract

The aim of the current study was to investigate the involvement of GABA neurotransmission in the CA1 region and endocannabinoid system in the basolateral amygdala (BLA) on morphine-induced memory impairment. We hypothesized that possible functional interaction between the GABAergic and cannabinoid systems in these brain regions would modulate morphine response in memory processing. Step-through type inhibitory avoidance paradigm was used for evaluating memory consolidation in adult male Wistar rats. Our results indicated that post-training systemic injection of morphine (3 and 5 mg/kg, i.p.) impaired memory retrieval. The microinjection of a GABA-A receptor agonist, muscimol (0.01-0.03 μg/rat) into the CA1 region increased the response of an ineffective dose of morphine (0.5 mg/kg, i.p.) and induced memory impairment, suggesting a synergistic interaction between morphine and muscimol. Interestingly, the activation of the BLA CB1 receptors by the microinjection of WIN55,212-2 (0.05-0.1 μg/rat) increased the effect of ineffective doses of muscimol (0.01 μg/rat; intra-CA1) and morphine (0.5 mg/kg, i.p.), inducing amnesia. The obtained results also showed that microinjection of AM251, a cannabinoid CB1 receptor antagonist, (1−2 μg/rat) into the BLA reversed the synergistic effect of muscimol and morphine, improving memory consolidation. It should be noted that the intra-CA1 microinjection of muscimol, intra-BLA microinjection of WIN55,212-2 or AM251 alone could not affect memory consolidation. Accordingly, it can be concluded that there may be a synergistic interaction between the CA1 GABAergic system and the BLA endocannabinoid neurotransmission with respect to the modulation of morphine-induced memory impairment. © 2020