Post-training Cannabinoid Administration Impairs 24-hour Consolidation of Rodent Spatial Memory

Cannabinoids are hypothesized to be an important neurotransmitter modulating memory loss by acting as an inhibitory retrograde messenger. Cannabinoid agonists are commonly found to be detrimental to normal learning and memory in a variety of tasks; however, often the drug is given prior to the memory task, making it difficult to deduce if pre-training infusion affects memory acquisition, consolidation, or retrieval selectively. Here rats were administered cannabinoids immediately following training in the hidden platform version of the Morris water task (MWT). Rat were given 8 massed trials, then immediately injected with either cannabinoid agonist WIN 55,212-2 (i.p., 3.7 mg/kg), cannabinoid antagonist AM251 (i.p., 3.7 mg/kg), or vehicle only.  Rats were also given a combination injection of antagonist plus agonist, either simultaneously or separated by 30 minutes. For all groups spatial memory retention was assessed 24 hrs later by a single non-reinforced probe and 4 trials of retraining. The findings suggest the cannabinoid agonist WIN 55,212-2 impaired memory acquisition and 24-hr consolidation, while the cannabinoid antagonist AM251 spared memory by blocking the effect of the agonist on consolidation.  Rats that received the cannabinoid agonist had poorer retention and memory for the platform location when compared to rats that received the cannabinoid antagonist or vehicle controls. The timing of the drug injections was found to be a critical variable. These findings indicate a role for CB₁ receptors in short-term consolidation of spatial memory, expanding the putative role of endogenous cannabinoids and CB₁ receptors in learning and memory.