Neuroscience
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Modulation of L-type Ca²⁺-channel function by dopamine is a major determinant of the rate of action potential firing by striatal medium spiny neurons. However, the role of these channels in modulating GABA release by nerve terminals in the basal ganglia is unknown. We found that depolarization-induced [³H]GABA release in both the substantia nigra reticulata and the external globus pallidus (GPe), was depressed by about 50% by either the selective L-channel dihydropyridine blocker nifedipine or the P/Q channel blocker ω-agatoxin TK. ⋯ In the GP nifedipine blocked the effects of D2 and A2(A) receptor coactivation as well as the effects of activating adenylyl cyclase with forskolin. ω-Agatoxin TK did not interfere with the action of these modulatory agents. The L-type Ca²⁺-channel agonist BAYK 8644 stimulated GABA release in both substantia nigra reticulata and GP. Because dihydropyridine sensitivity is a key criterion to identify L-type Ca²⁺-channel activity, our results imply that these channels are determinant of GABA release modulation by dopamine in striatonigral, striatopallidal and pallidonigral terminals.
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Neurochemical features in sympathetic and afferent neurons are subject to change during development. Nitric oxide (NO) plays a developmental role in the nervous system. To better understand the neuroplasticity of sympathetic and afferent neurons during postnatal ontogenesis, the distribution of neuronal NO synthase (nNOS) immunoreactivity was studied in the sympathetic para- and prevertebral, nodose ganglion (NG) and Th2 and L4 dorsal root ganglia (DRG) from female Wistar rats of different ages (newborn, 10-day-old, 20-day-old, 30-day-old, 2-month-old, 6-month-old, 1-year-old, and 3-year-old). nNOS-positive neurons were revealed in all sensory ganglia but not in sympathetic ones from birth onward. ⋯ In 10-day-old and older rats, the number of sensory nNOS-IR neurons binding IB4 reached more than 90% in DRG and more than 80% in NG. Only a small number of nNOS-positive cells showed immunoreactivity to calcitonin gene-related peptide, neurofilament 200, calretinin. The information provided here will also serve as a basis for future studies investigating mechanisms of the development of sensory neurons.
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Depressive patients show cognitive impairments that are strongly associated with cortisol levels and hippocampus functioning that interact via unknown mechanisms. In addition, a relation between depression and hippocampal synaptic plasticity was described. ⋯ These findings support the notion that increased levels of stress hormone act via the GR on hippocampal functioning and that, in this way, the cognitive deficits in mood disorders may be restored.
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This study was designed to examine the effect of voluntary exercise on hippocampal long-term potentiation (LTP) in morphine-dependent rats. The rats were randomly distributed into the saline-sedentary (Sal/Sed), the dependent-sedentary, the saline-exercise (Sal/Exc), and the dependent-exercise (D/Exc) groups. The Sal/Exc and the D/Exc groups were allowed to freely exercise in a running wheel for 10 days. ⋯ Moreover, the increase of PS-LTP in the morphine-exercise group was greater (22.5%), but not statistically significant, than that of the Sal/Exc group. These results may imply an additive effect between exercise and morphine on mechanisms of synaptic plasticity. Such an interaction between exercise and chronic morphine may influence cognitive functions in opiate addicts.
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Activity-dependent hyperpolarization of EGABA is absent in cutaneous DRG neurons from inflamed rats.
A shift in GABA(A) signaling from inhibition to excitation in primary afferent neurons appears to contribute to the inflammation-induced increase in afferent input to the CNS. An activity-dependent depolarization of the GABA(A) current equilibrium potential (E(GABA)) has been described in CNS neurons which drives a shift in GABA(A) signaling from inhibition to excitation. The purpose of the present study was to determine if such an activity-dependent depolarization of E(GABA) occurs in primary afferents and whether the depolarization is amplified with persistent inflammation. ⋯ The shift in E(GABA) was not blocked by 10 μM bumetanide. Furthermore, because activity-dependent hyperpolarization of E(GABA) was fully manifest in the absence of HCO₃⁻ in the bath solution, this shift was not dependent on a change in HCO₃⁻-Cl⁻ exchanger activity, despite evidence of HCO₃⁻-Cl⁻ exchangers in DRG neurons that may contribute to the establishment of E(GABA) in the presence of HCO₃⁻. While the mechanism underlying the activity-dependent hyperpolarization of E(GABA) has yet to be identified, because this mechanism appears to function as a form of feedback inhibition, facilitating GABA-mediated inhibition of afferent activity, it may serve as a novel target for the treatment of inflammatory pain.