Abstract
Cannabis has long been known to produce cognitive and emotional effects. Research has shown that cannabinoid drugs produce these effects by driving the brain’s endogenous cannabinoid system and that this system plays a modulatory role in many cognitive and emotional processes. This review focuses on the effects of endocannabinoid system modulation in animal models of cognition (learning and memory) and emotion (anxiety and depression). We review studies in which natural or synthetic cannabinoid agonists were administered to directly stimulate cannabinoid receptors or, conversely, where cannabinoid antagonists were administered to inhibit the activity of cannabinoid receptors. In addition, studies are reviewed that involved genetic disruption of cannabinoid receptors or genetic or pharmacological manipulation of the endocannabinoid-degrading enzyme, fatty acid amide hydrolase (FAAH). Endocannabinoids affect the function of many neurotransmitter systems, some of which play opposing roles. The diversity of cannabinoid roles and the complexity of task-dependent activation of neuronal circuits may lead to the effects of endocannabinoid system modulation being strongly dependent on environmental conditions. Recent findings are reviewed that raise the possibility that endocannabinoid signaling may change the impact of environmental influences on emotional and cognitive behavior rather than selectively affecting any specific behavior.
Highlights
Reviewed by: Viviana Trezza, University Roma Tre, Italy Patrizia Campolongo, Università degli Studi di Roma La Sapienza, Italy
This review focuses on the effects of endocannabinoid system modulation in animal models of cognition and emotion
The reasons for discrepancies are multiple, but an increasing number of publications suggest that the emotional effects of enhanced endocannabinoid signaling largely depend on environmental influences. These findings suggest that the anxiolytic effects, and possibly the antidepressant effects, of endocannabinoid signaling are enhanced under aversive conditions, which strengthens, rather than weakens, the putative usefulness of medications that enhance endocannabinoid signaling in the treatment of emotional disorders
Summary
EFFECTS OF CANNABINOID CB1 RECEPTOR AGONISTS AND ANTAGONISTS ON MEMORY ACQUISITION AND LONG-TERM MEMORY Water maze Much of the evidence that activating cannabinoid receptors can impair learning comes from studies using water maze procedures, which focus on spatial memory In these tests the animals are trained to find a submerged platform in a tank filled with opaque water. Acute systemic administration of Δ9-THC (8 mg/kg, IP) before the training session disrupts acquisition in the water maze test without affecting locomotion; this effect is prevented by the CB1 antagonist/inverse agonist rimonabant (DaSilva and Takahashi, 2002). When Acheson et al (2011) controlled for thigmotaxis, the impairing effects of WIN55212-2 were no longer detectable
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