Effects of the synthetic cannabinoid nabilone on spatial learning and hippocampal neurotransmission

Cannabinoids, the active components of marijuana, affect memory and hippocampal neurotransmission. It has been claimed that nabilone, a synthetic cannabinoid endowed with antiemetic properties, has a peculiar profile of actions. We studied the effects of the drug on spatial learning and in vitro hippocampal CA1 electrophysiology in the rat. Nabilone (0.1, 0.5, and 1.0 mg/kg ip) does not impair place learning in a water maze task, whereas Δ8-tetrahydrocannabinol (Δ8-THC) disrupts this function. At concentrations ranging from 1 nM to 10 μM nabilone does not influence basal glutamatergic neurotransmission, which is decreased by Δ8-THC. Although cannabinoids have been consistently reported to affect synaptic plasticity, nabilone 1 μM does not change paired-pulse facilitation, long-term potentiation and the magnitude of long-term depression. However, the time course of the latter phenomenon is significantly changed by the drug, the depression being lower than in control experiments from 7 to 35 min postinduction. Altogether, our data indicate that there might be differences in the effects of agonists for central cannabinoid receptors, which could help to understand the pharmacology of this class of molecules. The results also suggest that amnesia induced by cannabinoids be possibly related to their effects on hippocampal neurotransmission. The study supports the use of nabilone in conditions the course of which is complicated by cognitive impairment. © 2003 Elsevier Science Inc. All rights reserved.