Neuroscience
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Nociceptin receptors are densely distributed in the nucleus tractus solitarius pre- and postsynaptically. This study tested whether nociceptin receptors in this brain area are involved in the modulation of baroreceptor reflex. In pentobarbital-anesthetized rats, pharmacological activation of nociceptin receptors with bilateral microinjection of a synthetic peptide agonist, nociceptin, into the nucleus tractus solitarius attenuated baroreflex sensitivity as demonstrated by a marked reduction in baroreflex bradycardia induced by a single dose of intravenous phenylephrine. ⋯ In contrast, injection of an opioid receptor antagonist, naloxone (5nmol), did not modify the inhibition of baroreflex sensitivity induced by nociceptin. Neither nocistatin nor naloxone injected into the nucleus alone had any detectable effect on baseline blood pressure and heart rate and baroreflex bradycardia. These data indicate that the newly discovered nociceptin receptors in the central nervous system possess an inhibitory influence on baroreflex transmission at the level of the nucleus tractus solitarius.
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The effects of different hormone replacement regimens on basal forebrain cholinergic function were examined by measuring changes in choline acetyltransferase activity and high affinity choline uptake in adult, ovariectomized, rats. Increases in choline acetyltransferase activity were detected in the frontal cortex (20. 1%) and olfactory bulbs (30.4%) following two weeks, but not four weeks, of repeated treatment with estrogen plus progesterone. Increases in high affinity choline uptake were detected in the frontal cortex (39.5-55.1%), hippocampus (34.9-48.9%), and olfactory bulbs (29.9%) after two weeks, but not four weeks, of either continuous estrogen administration, repeated progesterone administration, or repeated treatment with estrogen plus progesterone. ⋯ The findings demonstrate that short-term treatment with estrogen and/or progesterone can significantly enhance cholinergic function within specific targets of the basal forebrain cholinergic projections. Most important is the fact that the effects varied considerably according to the manner and regimen of hormone replacement and did not persist with prolonged treatment. These findings could have important implications for the effective use of hormone replacement strategies in the prevention and treatment of Alzheimer's disease and age-related cognitive decline in women.
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The relation between serotonin release and electrical activity was examined in the nucleus raphe magnus of rats anesthetized with pentobarbital. Serotonin levels were monitored through a carbon-fiber microelectrode by fast cyclic voltammetry (usually at 1 Hz). Single-cell firing was recorded through the same microelectrode, except during the voltammetry waveform and associated electrical artifact (totaling about 30 ms). ⋯ Since serotonin levels and firing were usually inversely correlated, except near on(M) cells during pinch, we propose that serotonin is released from terminals of incoming nociceptive afferents. Prior neuroanatomical knowledge favors a midbrain origin for these afferents, while some of the drug findings suggest that their terminals possess inhibitory serotonergic autoreceptors, possibly of 5-HT1b subtype. The released serotonin could contribute to the inhibition of off(M) cells and excitation of on(M) cells by noxious stimulation, since inhibitory 5-HT1a receptors and excitatory 5-HT2 receptors, respectively, have previously been shown to dominate their serotonergic responses.
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In order to characterize the localization of the sigma(1) receptor in the adult rat central nervous system, a polyclonal antibody was raised against a 20 amino acid peptide, corresponding to the fragment 143-162 of the cloned sigma(1) receptor protein. Throughout the rostrocaudal regions of the central nervous system extending from the olfactory bulb to the spinal cord, intense to moderate immunostaining was found to be associated with: (i) ependymocytes bordering the entire ventricular system, and (ii) neuron-like structures located within the parenchyma. Double fluorescence studies confirmed that, throughout the parenchyma, sigma(1) receptor-immunostaining was essentially associated with neuronal structures immunostained for the neuronal marker betaIII-tubulin. ⋯ Electron microscope studies indicated that sigma(1) receptor immunostaining was mostly associated with neuronal perikarya and dendrites, where it was localized to the limiting plasma membrane, the membrane of mitochondria and of some cisternae of the endoplasmic reticulum. At the level of synaptic contacts, intense immunostaining was associated with postsynaptic structures including the postsynaptic thickening and some polymorphous vesicles, whereas the presynaptic axons were devoid of immunostaining. These data indicate that the sigma(1) receptor antibody prepared here, represents a promising tool for further investigating the role of sigma(1) receptors.
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Striatal nicotinic acetylcholine receptors with high affinity for nicotinic agonists are involved with the release of a number of neurotransmitters, including dopamine. Previous findings as to whether these receptors are changed in Parkinson's disease and Alzheimer's disease are inconsistent and no previous investigations have focused on these receptors in dementia with Lewy bodies and schizophrenia, which are also associated with disorders of movement. The present autoradiographic study of striatal [3H]nicotine binding in Alzheimer's and Parkinson's diseases, dementia with Lewy bodies and schizophrenia was conducted with particular reference to the potentially confounding variables of tobacco use and neuroleptic medication. [3H]Nicotine binding in both dorsal and ventral caudate and putamen was significantly reduced in Parkinson's disease (43-67%, n=13), Alzheimer's disease (29-37%, n=13) and dementia with Lewy bodies (50-61%, n=20) compared to age-matched controls (n=42). ⋯ In contrast, striatal [3H]nicotine binding in a group of elderly (56-85 years) chronically medicated individuals with schizophrenia (n=6) was elevated compared with the entire control group (48-78%, n=42) and with a subgroup that had smoked (24-49%, n=8). The changes observed in [3H]nicotine binding are likely to reflect the presence of these receptors on multiple sites within the striatum, which may be differentially modulated in the different diseases. Further study is warranted to explore which nicotinic receptor subunits and which neuronal compartments are involved in the changes in [3H]nicotine binding reported, to aid development of potential nicotinic receptor therapy.