Unconditioned and conditioned anxiogenic effects of the cannabinoid receptor agonist CP 55,940 in the social interaction test

In spite of the addictive properties of cannabinoids, under certain circumstances, they can evoke strong anxiogenic and aversive responses in humans and in animal tests of anxiety. Effects of different doses of CP 55,940 (10, 20, and 40 mug/kg) were tested in the low-light, familiar (LF) apparatus test condition of the social interaction test. The 40-mug/kg dose of CP 55,940 significantly decreased the time spent in social interaction, indicating an anxiogenic effect. This dose also had an independent effect of reducing locomotor activity. In rats tested undrugged 24 h after testing with 40 mug/kg, there was a significant anxiogenic effect, indicating conditioned anxiety. The group of rats injected with 40 mug/kg immediately after the social interaction test showed an unexpected significant anxiolytic effect when tested undrugged 24 h later. In an additional experiment, rats were tested in the high-light, familiar (HF) apparatus test condition after 10 or 40 mug/kg, and only those that were tested after 40 mug/kg showed an anxiogenic effect on the test day and a conditioned anxiogenic effect when tested undrugged 24 h later. Once again, those injected with 40 mug/kg after the social interaction test displayed an anxiolytic effect when tested undrugged 24 h later. We provide the first evidence for unconditioned and conditioned anxiogenic-like responses to a cannabinoid agonist in the social interaction test. (C) 2004 Elsevier Inc. All rights reserved.