Neuroscience
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Cocaine self-administration experiments were designed to assess the respective roles of D1-like and D2-like dopamine receptors in the ventral forebrain in cocaine reinforcement. D1-like or D2-like dopamine receptor antagonists were microinjected into the nucleus accumbens core, nucleus accumbens shell, neostriatum or lateral septum prior to sessions in which cocaine was self-administered under a progressive ratio schedule by rats. ⋯ Neither SCH-23390 nor eticlopride influenced cocaine reinforcement when administered into the neostriatum or lateral septum. Collectively, these results indicate that D1-like and D2 dopamine receptors in the nucleus accumbens shell selectively modulate the reinforcing efficacy of cocaine, whereas D1-like and D2 dopamine receptors in the accumbens core have a more general influence on reinforced behaviors.
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Effects of i.c.v. and i.t. administration of (3SR,4aRS,6RS,8aRS)-6-[2-(1H-tetrazol-5-yl)ethyl]decahydroisoquinoline-3-carboxylic acid (LY215490), a competitive alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist and MK-801, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist on the micturition reflex were evaluated in urethane-anesthetized rats, to determine if glutamatergic mechanisms in brain as well as spinal cord are important for the control of micturition. I.c.v. or i.t. injection of LY215490 in low doses (0.01-0.03 microg) did not change rhythmic bladder or external urethral sphincter (EUS) electromyogram (EMG) activity during continuous cystometrograms (CMGs; 0.21 ml/min), whereas higher doses (0.1-1 microg) markedly suppressed these responses. During single CMGs (0.04 ml/min), 0.1-1 microg i.c.v. or 0.1-10 microg i.t. doses increased volume threshold and pressure threshold for inducing micturition, and decreased bladder contraction amplitude and voiding efficiency. ⋯ Pretreatment i.c.v. with MK-801 in a dose 1.8 microg which alone had little effect on bladder contraction amplitude and EUS EMG activity, markedly enhanced depressant effects of LY215490 (0.03 microg i.c.v.) on these responses. Administration of same doses of drugs by i.t. route did not elicit a similar synergistic interaction. These data indicate that in urethane-anesthetized rats glutamatergic mechanisms in brain and spinal cord are essential for controlling micturition and that interactions between AMPA and NMDA glutamatergic transmission are important at supraspinal but not spinal sites.
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The central nucleus of the amygdala (Ce) and the bed nucleus of the stria terminalis (BST) are key structures of the extended amygdala, which is suggested to be involved in drug addiction and reward. We have previously reported that the Ce plays a crucial role in the negative affective component of morphine withdrawal. In the present study, we examined the involvement of the neural pathway between the Ce and the BST in the negative affective component of morphine withdrawal in rats. ⋯ Bilateral excitotoxic lesion of the Ce reduced the number of morphine withdrawal-induced c-Fos-immunoreactive neurons in the lateral and medial BST, with significant decreases in the posterior, ventral and juxtacapsular parts of lateral division, and anterior part of the medial division, but not in the ventral part of the medial division of the BST. On the other hand, bilateral excitotoxic lesion of the BST had no effect on such c-Fos induction within the capsular part, nor the ventral and medial divisions of the Ce. These results suggest that activation of the BST mediated through the neural pathway from the Ce contributes to the negative affective component of morphine withdrawal.
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Taste receptor cells are primary sensory receptors utilized by the nervous system to detect the presence of gustatory stimuli in the oral cavity. These cells are particularly heterogeneous and may be divided into various subtypes based on morphological, histochemical, or physiological criteria. One example is the heterogeneous expression of neuropeptides, such as cholecystokinin and vasoactive intestinal polypeptide. ⋯ More remarkable was the observation that these two peptides displayed almost identical expression patterns with these signal transduction molecules, suggesting that peptides are not randomly expressed with relation to signal transduction molecules. This observation supports the hypothesis that peptides may play roles in transduction. Further physiological exploration will be required to elucidate the nature of these roles.
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The role of p38 and c-jun-N-terminal kinases 1/2, members of the mitogen-activated protein kinase family, in mediating the toxic effects of human immunodeficiency virus-1 transactivator of transcription (Tat) and gp120 were explored in primary mouse striatal neurons in vitro. Both Tat and gp120 caused significant increases in p38 and c-jun-N-terminal kinase mitogen-activated protein kinase phosphorylation, caspase-3 activity, neurite losses and cell death in striatal neurons. ⋯ Alternatively, gp120-induced increases in caspase-3 activity, neurite losses and neuronal death were prevented by p38, but not c-jun-N-terminal kinase, mitogen-activated protein kinase inhibition. Our findings suggest that gp120 induces neuronal dysfunction and death through actions at p38 mitogen-activated protein kinase, while Tat kills neurons through actions that are independent of p38 or c-jun-N-terminal kinase mitogen-activated protein kinase, or through the concurrent activation of multiple proapoptotic pathways.