1. Neuropharmacology. 2010 Nov;59(6):503-10. Epub 2010 Jul 13.

Revisiting the complex influences of cannabinoids on motor functions unravels
pharmacodynamic differences between cannabinoid agonists.

Bosier B, Sarre S, Smolders I, Michotte Y, Hermans E, Lambert DM.

Unité de Chimie Pharmaceutique et de Radiopharmacie, Université Catholique de
Louvain, B-1200 Brussels, Belgium.

While numerous cannabinoid ligands were historically characterized using the
tetrad test (hypomobility, catalepsy, hypothermia, analgesia), only few studies
have extensively compared HU 210 and CP 55,940 which are nowadays classically
used as reference agonists. Therefore, we herein re-examined the acute and the
sustained changes in motor activities mediated by these two agonists in adult
rats. As expected for cannabinoid agonists, exposure to either HU 210 or CP
55,940 induced a marked reduction in spontaneous locomotion. This reduction
observed as early as 15 min after injection was correlated with the typical
rearing and cataleptic responses, and was reversed by co-administration of the
CB(1) cannabinoid receptor antagonist SR 141716A. Nevertheless, HU 210, but not
CP 55,940, was found to induce persistent responses, lasting for at least 24h.
Also suggesting the involvement of additional targets for HU 210, 10mg/kg SR
141716A failed to reverse the persistent HU 210-mediated decline in locomotion
and rearing, while 1mg/kg was sufficient to completely abolish the behavioural
responses measured 6h after the injection. Beside pharmacokinetic differences,
these data therefore denote distinct pharmacodynamic profiles for HU 210 and CP
55,940. Together, these results suggest that HU 210 displays multicomponent
responses that should be taken into account when interpreting data from in
vivo/ex vivo studies.


PMID: 20633567 [PubMed - in process]