Abstract
Memory extinction is referred to as a learning process in which a conditioned response (CR) progressively reduces over time as an animal learns to uncouple a response from a stimulus. Extinction occurs when the rat is placed into a context without shock after training. Docosahexaenoic acid (DHA, C22:6, n-3) is implicated in memory formation in mammalian brains. In a two-way active shuttle-avoidance apparatus, we examined whether DHA affects the extinction memory and the expression of brain cognition-related proteins, including gastrin-releasing peptide receptor (GRPR), brain-derived neurotrophic factor receptor (BDNFR) tyrosine kinase receptor B (TrKB), and N-methyl-d-aspartate receptor (NMDAR) subunits NR2A and NR2B. Also, the protein levels of GRP, BDNF, postsynaptic density protein-95 (PSD-95), and vesicular acetylcholine transporter (VAChT), and the antioxidative potentials, in terms of lipid peroxide (LPO) and reactive oxygen species (ROS), were examined in the hippocampus. During the acquisition phase, the rats received a conditioned stimulus (CS-tone) paired with an unconditioned stimulus (UCS foot shock) for three consecutive days (Sessions S1, S2, and S3, each consisting of 30-trials) after 12 weeks of oral administration of DHA. After a three-day interval, the rats were re-subjected to two extinction sessions (S4, S5), each comprising 30 trials of CS alone. During the acquisition training in S1, the shock-related avoidance frequency (acquisition memory) was significantly higher in the DHA-administered rats compared with the control rats. The avoidance frequency, however, decreased with successive acquisition trainings in sessions S2 and S3. When the rats were subjected to the extinction sessions after a break for consolidation, the conditioned response (CR) was also significantly higher in the DHA-administered rats. Interestingly, the freezing responses (frequency and time) also significantly decreased in the DHA-administered rats, thus suggesting that a higher coping capacity was present during fear stress in the DHA-administered rats. DHA treatments increased the mRNA levels of GRPR, BDNF receptor TrKB, and NMDAR subunit NR2B. DHA also increased the protein levels of GRP, BDNF, PSD-95, and VAChT, and the antioxidative potentials in the hippocampus. These results suggest the usefulness of DHA for treating stress disorders.
Highlights
We have previously reported that docosahexaenoic acid (DHA, C22:6 n-3) augments spatial memory acquisition [1], stimulates neurogenesis [2], protects [3] and improves [4] memory impairments of amyloid β peptide1–40 -infused Alzheimer’s disease (AD) model rats by decreasing amyloidogenesis [5,6], and protects age-related cognitive decline in the elderly [7]
There were no significant differences in body weight and/or food intake between the rat groups (BW: Control group: 371 ± 29 g; DHA group: 380 ± 20 g; Food intake per day: Control group, 22.3 ± 2.5 g; DHA group, 24.1 ± 3.0 g)
The current study indicates that increased levels of these memory-related substrates in the DHA rats may be involved in the improved expression of fear memory acquisition
Summary
We have previously reported that docosahexaenoic acid (DHA, C22:6 n-3) augments spatial memory acquisition [1], stimulates neurogenesis [2], protects [3] and improves [4] memory impairments of amyloid β peptide1–40 -infused Alzheimer’s disease (AD) model rats by decreasing amyloidogenesis [5,6], and protects age-related cognitive decline in the elderly [7]. These results and Molecules 2018, 23, 451; doi:10.3390/molecules23020451 www.mdpi.com/journal/molecules. The mechanisms through which the molecule DHA affects anxiety, stress, and fear memory remain unclear.
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