The influence of cannabinoids on neural transmission and behavior has become more evident in recent years. Despite this, virtually nothing is currently known about the effects of carmabinoids on emotional (fear) learning and memory. Using a classical fear conditioning paradigm, we have recently found that cannabinoid receptor activation selectively impairs the acquisition and the expression of contextual fear conditioning while sparing, in the same rats, the acquisition and expression of fear responses to an acoustic stimulus that was paired with mild footshock. There is a paucity of direct evidence, however, linking cannabinoid receptors in specific brain regions to fear-related learning. Thus, the goal of the proposed work is to determine where cannabinoids act in the brain to interfere with both the acquisition and the expression of contextual fear learning. Fifteen minutes prior to Pavlovian fear conditioning (tone-shock trials) or behavioral testing, rats will receive bilateral infusions of a cannabinoid receptor agonist or vehicle into the dorsal hippocampus, nucleus accumbens, basolateral amygdala, or central nucleus of the amygdala. Each of these brain regions contains a moderate-to-high density of cannabinoid receptors and is important for contextual fear conditioning. Twenty-four and forty-eight hours later, behavioral fear responses (i.e., freezing responses) to the conditioning context and to the tone will be measured. One of the long-term objectives of this research is to understand how commonly abused drugs such as cannabinoids influence the neural transmission, and possibly the plasticity underlying emotional learning and memory. Finally, it is our hope that this research will help elucidate some of the ways in which endocannabinoids influence emotional learning and memory processes. This could have important implications for the development of anxiety disorders, which are believed to be the result of a malfunction in neural circuits that mediate fear learning.
