Behavioural brain research
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Over the last decade accumulating evidence suggests that brain dopamine (DA) has a role in depression, particularly given the high comorbidity of depression with Parkinson's Disease (PD) and the antidepressant effects of the DA receptor subtype 3 (D3R) agonist pramipexole. The present study assesses the role of D3R in depression. Here we hypothesized that D3R mediates the antidepressant effects of DA. ⋯ Whereas D3R deficient mice did not show significant alterations in locomotion when tested in the openfield, these animals showed anxiety-like symptoms measured as a significant increase in thigmotaxis at the openfield and a significantly lower time spent in the lit compartment at the light/dark exploration test. D3RKO animals also showed depressive-like symptoms as measured by increased immobility time in the Porsolt forced swim test and the tail suspension test, as well as anhedonia measured in the non-motor dependent sucrose test. In conclusion, D3R deficiency results in anxiety-like and depressive-like symptoms that cannot be attributed to motor dysfunction.
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Within the Pavlovian conditioning framework, extinction is a procedure in which, after conditioning, the conditioned stimulus (CS) is repeatedly presented without the unconditioned stimulus (US). During this procedure the conditioned response (CR) is gradually attenuated. It has been suggested that extinction during the early stages of ontogeny is a qualitatively different process from extinction in adulthood: during infancy, extinction may result in erasure of the memory, while during adulthood extinction involves new learning. ⋯ Extinction produced changes in the expression of freezing, grooming and exploration, and the clearest evidence of spontaneous recovery came from the analysis of freezing behavior. The pattern of behavior observed during extinction is compatible with theoretical approaches which consider different dynamic behavioral systems, and it also fit in well with a molar approach to the analysis of behavior, which considers that extinction involves a transition from one allocation of time among behaviors to another allocation, rather than a loss of strength in any particular discrete response. These results have implications for the study of extinction during infancy, since they are compatible with the hypothesis that the original memory survives extinction, and highlight the importance of control conditions for detecting this effect during this ontogenetic period.
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The effects of curcumin on depressive-like behavior in mice after lipopolysaccharide administration.
Current evidence supports that inflammation and increased cytokine levels are associated with depression-like symptoms and neuropsychological disturbances in humans. Curcumin has anti-inflammatory, antioxidant and anti-depressant-like properties. Here, we examined the effects of curcumin on lipopolysaccharide (LPS)-induced depressive-like behavior and inflammation in male mice. ⋯ Moreover, pre-treatment with curcumin attenuated LPS-induced microglial activation and overproduction of pro-inflammatory cytokine (interleukin-1β and tumor necrosis factor-α), as well as the levels of inducible nitric oxide synthase and cyclooxygenase-2 mRNA in the hippocampus and prefrontal cortex (PFC). In addition, curcumin ameliorated LPS-induced NF-κB activation in the hippocampus and PFC. The results demonstrate that curcumin may be an effective therapeutic agent for LPS-induced depressive-like behavior, partially due to its anti-inflammatory aptitude.
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Aging is associated with impaired learning and memory accompanied by reductions in adult hippocampal neurogenesis and brain expression of neurotrophic factors among other processes. Epigallocatechin-3-gallate (EGCG, a green tea catechin), β-alanine (β-ala, the precursor of carnosine), and exercise have independently been shown to be neuroprotective and to reduce inflammation and oxidative stress in the central nervous system. We hypothesized that EGCG, β-ala supplementation or exercise alone would improve learning and memory and increase neurogenesis in aged mice, and the combined intervention would be better than either treatment alone. ⋯ VWR increased the number of BrdU cells in the dentate gyrus, increased expression of brain-derived neurotrophic factor, decreased expression of the inflammatory cytokine interleukin-1β, and improved performance in the MWM and CFC tests. The dietary intervention reduced brain oxidative stress as measured by 4-hydroxynonenal in the cerebellum, but had no effect on BrdU labeling or behavioral performance. These results suggest that exercise, but not a diet containing EGCG and β-ala, exhibit pro-cognitive effects in aged mice when given at these doses in this relatively short time frame.
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We previously found that juvenile pituitary adenylate cyclase-activating polypeptide (PACAP)-knockout (PACAP(-/-)) mice reared in an enriched environment (EE) for 4 weeks showed attenuated hyperactivity, jumping behavior, impairments in social interaction, and depression-like behavior. The present study examined the effects of EE on memory function and memory-related protein levels in PACAP(-/-) mice. Eight-week-old PACAP(-/-) mice displayed fear memory dysfunction in a contextual fear conditioning test and cognitive impairments in a novel object recognition test. ⋯ Increased levels of NR2B, phospho-ERK, phospho-CaMKII and BDNF were not observed 2 weeks after a return to housing in a SE. These findings suggest that living in an EE engenders long-lasting reductions in memory impairments in PACAP(-/-) mice. The present study also implies that increases in hippocampal memory-related protein and BDNF levels are responsible for the beneficial effects of an EE, but not for the maintenance of these effects.