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Enhanced LTP in aged rats: detrimental or compensatory?
Pinho, Júlia; Vale, Ruben; Batalha, Vânia; Costenla, Ana Rita; Dias, Raquel Baptista; Rombo, Diogo M.; Sebastião, Ana M; De Mendonça, AlexandreAge-dependent memory deterioration has been well documented and yet an increase in rat hippocampal LTP upon aging has been reported. This poses the question of whether the enhanced LTP is a cause or an attempt to compensate the memory deficits described in aged rats. Hippocampal slices from young, adult and aged Wistar rats were pre-incubated, with an NMDA receptor (NMDAR) antagonist, memantine (1 μM, 4 h), and...
Maternal separation impairs long term-potentiation in CA1-CA3 synapses and hipp...
Sousa, Vasco C.; Vital, Joana; Costenla, Ana Rita; Batalha, Vânia; Sebastião, Ana M; Ribeiro, Joaquim A.; Lopes, Luisa V.Exposure to chronic stress during the neonatal period is known to induce permanent long-term changes in the central nervous system and hipothalamic-pituitary-adrenal axis reactivity that are associated with increased levels of depression, anxiety, and cognitive impairments. In rodents, a validated model of early life stress is the maternal separation (MS) paradigm, which has been shown to have long-term consequ...
Enhanced role of adenosine A2A receptors in the modulation of LTP in the rat hi...
Costenla, Ana Rita; Diógenes, Maria José; Canas, Paula M.; Rodrigues, Ricardo J.; Nogueira, Célia; Marôco, João; Agostinho, Paula M.Adenosine neuromodulation depends on a balanced activation of inhibitory A₁ (A₁R) and facilitatory A(₂A) receptors (A(₂A) R). Both A₁ R and A(₂A) R modulate hippocampal glutamate release and NMDA-dependent long-term potentiation (LTP) but ageing affects the density of both A₁ R and A(₂A) R. We tested the effects of selective A₁ R and A(2A) R antagonists in the modulation of synaptic transmission and plasticity ...
Caffeine, adenosine receptors, and synaptic plasticity
Costenla, Ana Rita; Cunha, Rodrigo A.; De Mendonça, AlexandreFew studies to date have looked at the effects of caffeine on synaptic plasticity, and those that did used very high concentrations of caffeine, whereas the brain concentrations attained by regular coffee consumption in humans should be in the low micromolar range, where caffeine exerts pharmacological actions mainly by antagonizing adenosine receptors. Accordingly, rats drinking caffeine (1 g/L) for 3 weeks, d...
Adenosine A3 receptors in the rat hippocampus: Lack of interaction with A1 rece...
Lopes, Luísa V.; Rebola, Nelson; Costenla, Ana Rita; Halldner, Linda; Jacobson, Marlene A.; Oliveira, Catarina R.; Richardson, Peter J.Adenosine acts as a neuromodulator in the hippocampus essentially through activation of inhibitory A1 receptors. Using single-cell PCR analysis, we found that CA1 pyramidal cells coexpress A1 receptor mRNA together with that of another adenosine receptor, the A3 receptor. As occurs for the A1 receptor, Western blot analysis indicated that the A3 receptor is also located in hippocampal nerve terminals. However, ...
Persistence of the neuromodulatory effects of adenosine on synaptic transmissio...
De Mendonça, Alexandre; Costenla, Ana Rita; Ribeiro, Joaquim A.Adenosine modulates long-term potentiation (LTP) and long-term depression (LTD) in the hippocampus. We tested whether induction of LTP or LTD might reciprocally modify the role of adenosine as an inhibitory modulator of synaptic transmission in the hippocampus. The experiments were performed on hippocampal slices of the rat. Two separate sets of the Schaffer pathway were alternately stimulated. Evoked field exc...
Effects of Carbamazepine and novel 10,11-Dihydro-5H-Dibenz(b,f)Azepine-5-Carbox...
Cunha, Rodrigo A.; Coelho, Joana E; Costenla, Ana Rita; Lopes, Luisa V.; Parada, António; De Mendonça, Alexandre; Sebastião, Ana M; Ribeiro, Joaquim A.The effects of carbamazepine on synaptic transmission in rat hippocampal slices were compared with those of two novel analogues (BIA2-093 and BIA2-024) with equivalent anticonvulsant efficacy but with fewer side effects. Carbamazepine (10-1000 microM) inhibited in a concentration-dependent manner the field excitatory postsynaptic potential (fPSP) response, with an EC50 of 263 microM, and also attenuated the pre...