The microinjection of a cannabinoid agonist into the accumbens shell induces anxiogenesis in the elevated plus-maze.

Abstract This study investigated the effect of a cannabinoid agonist injected into the shell region of the nucleus accumbens (nAcb shell) on anxiety-related behaviors. The animals (male Wistar rats) were unilaterally microinjected with either ACEA (arachidonyl-2′-chloroethylamide a CB1 receptor agonist) at doses of 0.005, 0.05 or 0.5 pmol, or vehicle (ethanol 0.04% in saline 0.9%) and submitted to the elevated plus-maze (EPM), a pre-clinical test of anxiety. The data showed that rats microinjected with ACEA (0.05 pmol/0.2 μl) into the nAcb shell exhibited decreased % open arm time and open arm entries in comparison with the control group, which is compatible with an anxiogenic-like effect. To rule out the hypothesis that spread of the drug into the ventricle was responsible for the observed anxiogenic effect, 0.05 pmol ACEA was injected into the lateral ventricle and shown not to alter the responses representative of fear/anxiety and locomotion. The locomotor activity was not changed at the dose of 0.05 pmol ACEA microinjected into the nAcb shell. The present data suggest that activation of cannabinoid receptors in the nAcb shell may modulate fear/anxiety in the EPM.