Deficient endocannabinoid signaling in the central amygdala contributes to alcohol dependence-related anxiety-like behavior and excessive alcohol intake

Antonia Serrano, Francisco J. Pavon, Matthew W. Buczynski, Joel Schlosburg, Luis A. Natividad, Ilham Y. Polis, David G. Stouffer, Eric P. Zorrilla, Marisa Roberto, Benjamin F. Cravatt, Rémi Martin-Fardon, Fernando Rodriguez de Fonseca and Loren H. Parsons  (April 2018)

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Negative emotional states that are associated with excessive alcohol intake, particularly anxiety-like states, have been linked to opponent processes in the central nucleus of the amygdala (CeA), affecting stress-related transmitters and monoamines. This study extends these observations to include endocannabinoid signaling in alcohol-dependent animals.

Role of endocannabinoids in innate fear

Carsten T. Wotjak  (September 2017)

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Most of our current knowledge about the neuroanatomical, neurochemical and molecular basis of fear results from Pavlovian fear conditioning. Much less is known about the underpinnings of innate fear responses, which share higher face validity with human anxiety disorders such as agoraphobia, acrophobia and panic attacks. I will introduce our recently established new test paradigms, which allow us to study acrophobic/agoraphobic behavior and the transition between passive and active fear as a function of threat proximity.

Endocannabinoids, Stress, and Negative Affect

Anthony L. Berger, Angela M. Henricks, Matthew N. Hill, Ryan J. McLaughlin  (May 2017)

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The stress response is an evolutionarily conserved mechanism to both allow an organism to cope with a threat and to restore homeostasis following exposure to a stressor. With respect to this response, preclinical research demonstrates that the endogenous cannabinoid (ECB) system constrains the hypothalamic-pituitary-adrenal axis and plays a major role in the habituation to stressors.

Don’t Worry, Be Happy: Endocannabinoids and Cannabis at the Intersection of Stress and Reward

Nora D. Volkow, Aidan J. Hampson, and Ruben D. Baler  (January 2017)

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Cannabis enables and enhances the subjective sense of well-being by stimulating the endocannabinoid system (ECS), which plays a key role in modulating the response to stress, reward, and their interactions. However, over time, repeated activation of the ECS by cannabis can trigger neuroadaptations that may impair the sensitivity to stress and reward. This effect, in vulnerable individuals, can lead to addiction and other adverse consequences. The recent shift toward legalization of medical or recreational cannabis has renewed interest in investigating the physiological role of the ECS as well as the potential health effects, both adverse and beneficial, of cannabis. Here we review our current understanding of the ECS and its complex physiological roles.

The endocannabinoid system in anxiety, fear memory and habituation

S Ruehle, A Aparisi Rey, F Remmers, and B Lutz  (January 2012)

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Evidence for the involvement of the endocannabinoid system (ECS) in anxiety and fear has been accumulated, providing leads for novel therapeutic approaches. In anxiety, a bidirectional influence of the ECS has been reported, whereby anxiolytic and anxiogenic responses have been obtained after both increases and decreases of the endocannabinoid tone. The recently developed genetic tools have revealed different but complementary roles for the cannabinoid type 1 (CB1) receptor on GABAergic and glutamatergic neuronal populations. This dual functionality, together with the plasticity of CB1 receptor expression, particularly on GABAergic neurons, as induced by stressful and rewarding experiences, gives the ECS a unique regulatory capacity for maintaining emotional homeostasis.