The acute treatment with CB1 cannabinoid receptors agonists modulate the AChE activity at basal forebrain cholinergic projections

Moreno, M. , Llorente, A. , Manuel, I. . , Giralt, M. T. & Rodríguez, R. .

University of the Basque Country (UPV-EHU)

The loss of cholinergic neurons and muscarinic receptors (MR) at the basal forebrain (B) has been reported in Alzheimer´s disease. Moreover, the administration of the MR antagonist, scopolamine (Scop), causes memory impairment in the rat. Controversial data have been reported about the role of cannabinoids in cognitive functions.

We evaluated the acute effect of WIN55,212-2 (1 mg/kg; i.p.) in the acetilcholinesterase (AChE) activity at basal forebrain cholinergic projections following the administration of Scop (2 mg/kg; i.p.) to rats. Passive avoidance test was used to evaluate learning and memory. [35S]GTP(Gamma)S autoradiography was used to measure the functional activity of MR and CB1 receptors at B projections. The different assays were correlated with each other. The obtained data showed an increase in AChE activity in the Scop group in several hippocampal areas that was reverted by the cannabinoid agonist (% Scop over control; CA1 Lmol (dorsal): 51±6, CA1 Lmol (ventral): 53 ± 14, CA1 Py (ventral): 27±7, CA2 Rad (dorsal): 20 ± 8, Mo DG: 53 ± 14, Po DG: 53 ± 14). These evidences support the existence of an interaction between cholinergic and cannabinoid systems in brain areas related to learning and memory.