Study of the neurobiological mechanisms underlying the effects of delta9-tetrahydrocannabinol on hippocampal memory and plasticity

Abstract

Cannabis is one of the most consumed illicit drugs worldwide mainly for recreational purposes. Nowadays the interest of cannabis and its derivatives for therapeutic purposes is increasing, and controversy concerning its beneficial and detrimental effects have been prominent in society. In this Thesis we used murine models to study the structural, functional, and molecular mechanisms involved in THC detrimental effects on hippocampal memory. Specifically, we reported that a single exposure to THC alters the proteasome system, a key component in cell protein homeostasis. Moreover, we described how a single exposure to THC is sufficient to transiently alter hippocampal structural plasticity and the phosphorylation state of plasticity related proteins. Finally, we characterized the effect of a repeated exposure to a non-amnesic low dose of THC on memory and structural and functional plasticity. Overall, we combined behavioral and biochemical approaches to advance in the knowledge of the neurobiological mechanisms underlying the memory impairment produced by THC.