Effects of omega-3 polyunsaturated fatty acids on psychophysiological symptoms of post-traumatic stress disorder in accident survivors: A randomized, double-blind, placebo-controlled trial

Acquisition and storage of aversive memories is one of the basic principles of central nervous systems throughout the animal kingdom. In the absence of reinforcement, the resulting behavioural response will gradually diminish to be finally extinct. Despite the importance of extinction, its cellular mechanisms are largely unknown. The cannabinoid receptor 1 (CB1) and endocannabinoids are present in memory-related brain areas and modulate memory. Here we show that the endogenous cannabinoid system has a central function in extinction of aversive memories. CB1-deficient mice showed strongly impaired short-term and long-term extinction in auditory fear-conditioning tests, with unaffected memory acquisition and consolidation. Treatment of wild-type mice with the CB1 antagonist SR141716A mimicked the phenotype of CB1-deficient mice, revealing that CB1 is required at the moment of memory extinction. Consistently, tone presentation during extinction trials resulted in elevated levels of endocannabinoids in the basolateral amygdala complex, a region known to control extinction of aversive memories. In the basolateral amygdala, endocannabinoids and CB1 were crucially involved in long-term depression of GABA (gamma-aminobutyric acid)-mediated inhibitory currents. We propose that endocannabinoids facilitate extinction of aversive memories through their selective inhibitory effects on local inhibitory networks in the amygdala. Show more

The beta-adrenergic blocker propranolol given within hours of a psychologically traumatic event reduces physiologic responses during subsequent mental imagery of the event. Here we tested the effect of propranolol given after the retrieval of memories of past traumatic events. Subjects with chronic post-traumatic stress disorder described their traumatic event during a script preparation session and then received a one-day dose of propranolol (n=9) or placebo (n=10), randomized and double-blind. A week later, they engaged in script-driven mental imagery of their traumatic event while heart rate, skin conductance, and left corrugator electromyogram were measured. Physiologic responses were significantly smaller in the subjects who had received post-reactivation propranolol a week earlier. Propranolol given after reactivation of the memory of a past traumatic event reduces physiologic responding during subsequent mental imagery of the event in a similar manner to propranolol given shortly after the occurrence of a traumatic event. Show more

Acquired memory initially depends on the hippocampus (HPC) for the process of cortical permanent memory formation. The mechanisms through which memory becomes progressively independent from the HPC remain unknown. In the HPC, adult neurogenesis has been described in many mammalian species, even at old ages. Using two mouse models in which hippocampal neurogenesis is physically or genetically suppressed, we show that decreased neurogenesis is accompanied by a prolonged HPC-dependent period of associative fear memory. Inversely, enhanced neurogenesis by voluntary exercise sped up the decay rate of HPC dependency of memory, without loss of memory. Consistently, decreased neurogenesis facilitated the long-lasting maintenance of rat hippocampal long-term potentiation in vivo. These independent lines of evidence strongly suggest that the level of hippocampal neurogenesis play a role in determination of the HPC-dependent period of memory in adult rodents. These observations provide a framework for understanding the mechanisms of the hippocampal-cortical complementary learning systems. Show more