Abstract
AbstractBackgroundAlzheimer’s disease (AD) is associated with a selective vulnerability of basal forebrain cholinergic neurons (BFCN). The endocannabinoid (eCB) system modulates those BFCN pathways in AD. However, the effect of cannabinoid compounds on memory and learning remains controversial. Therefore, we evaluate the effect of cannabinoid agonists in recognition learning and memory in rats with a specific lesion of BFCN.MethodSprague‐Dawley male rats were infused bilaterally in the BFCN with 192IgG‐saporin toxin, (SAP group, n=10). Another group of SAP rats was treated with CB1 receptor agonist WIN 55,212‐2 for 5 days (SAP+WIN, n=10). Memory and learning were evaluated by Novel Object Recognition Task (NORT). The ability to identify new objects in the short term (3h after learning) and the long term (24h after learning), and other exploratory parameters, were measured.ResultIn the short term, control group and SAP group spent significantly more time exploring the new object than the old one (CON: 68.37% ± 4.05, p>0.01 and SAP: 60.72% ± 2.86, p>0.01), while SAP+WIN group did not (50.42% ± 5.73). In the long term, control group spent significantly more time exploring the new object than the old one (70.81% ± 2.42, p>0.001), but SAP group failed to do so (54.85% ± 3.93). Interestingly, SAP+WIN rats also spent more time exploring the new object than the old one (60.37% ± 6.36, p>0.05). Moreover, SAP group showed an increased exploratory behavior compared to control group, measured by the total exploration time in the long term (SAP: 49.76s ± 5.36 vs CON: 26.51s ± 4.45, p>0.05) and the number of rearings performed (SAP: 30.5 ± 2.4 vs CON: 21.3 ± 2.3, p>0.05). WIN 55,212‐2 treatment did not modify these latter parameters.ConclusionThese results suggest that degeneration of BFCN pathways does not impair learning in NORT test, but impairs memory consolidation. A sub‐chronic treatment with WIN 55,212‐2 was able to restore memory in rats with a BFCN lesion, even if it induces attention deficits at the short term. Thus, we suggest that cannabinoid agonists might be a plausible treatment for the typical contextual recognition problems derived from BFCN impairment in AD patients.
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