Neuroscience
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Rats exposed to repeated unavoidable stress show decreased dopamine output in the nucleus accumbens shell (NAcS) and do not acquire vanilla sugar (VS)-sustained appetitive behavior (VAB). Rats treated with lithium for 3 weeks also show decreased NAcS dopamine output, yet they acquire VAB. Feeding a novel palatable food increases extraneuronal dopamine levels in the NAcS and medial prefrontal cortex (mPFC) in rats. ⋯ The first group showed a lower dopaminergic response to VS consumption than the control group, but the latter showed no dopaminergic response in the NAcS and mPFC. We propose that the limbic dopaminergic response to a novel palatable food plays a role in associative learning and that it is predictive of the competence to learn an appetitive behavior. Moreover, in our experimental conditions a phasic increase in mesolimbic dopamine no longer signals the VS stimulus once it has become a reinforcer in an appetitive task.
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To investigate developmental changes in neurosteroid modulation of GABA(A) receptors, whole-cell currents were elicited by applying GABA with allopregnanolone or pregnenolone sulfate (PS) to dentate granule cells (DGCs), acutely isolated from 7-14-day-old and adult rats. GABA evoked larger currents from dentate granule cells acutely isolated from adult rats (adult DGCs) than from neonatal DGCs, due to increased efficacy (1662+/-267 pA in adult DGCs versus 1094+/-198 pA in neonatal DGCs, P=0.004), and current density (0.072+/-0.01 pA/microm(2) in neonatal rat DGCs to 0.178+/-0.02 pA/microm(2) in adult DGCs), but unchanged potency (EC(50) was 18.5+/-2 microm in adult DGCs, and 26.6+/-7.9 microm in neonatal DGCs, P=0.21). Allopregnanolone sensitivity of GABA(A) receptor currents increased during development due to an increased potency (21.1+/-4.7 nM in adult DGCs versus 94.6+/-9 nM in neonatal DGCs, P=0.0002). ⋯ This demonstrated that cell bodies and dendrites of granule cells are moderately positive for the alpha1 staining in adult rats but weakly so in neonatal rats. Higher-magnification images demonstrate large number of clusters of alpha1-subunit in the cell bodies of dentate granule cells of adult rat but rare clusters in granule cells of neonatal rats. Maturation of GABA(A) receptors in DGCs is characterized by increased number of GABA(A) receptors that are more sensitive to endogenous neurosteroid allopregnanolone, which might be related to increased expression of alpha1 subunit.
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Since metabolic neural activity is accompanied by heat release, measurement of local brain temperature offers a method for assessing alterations in neural activity. This approach, continuous monitoring of local brain (ventral tegmental area, ventral striatum, and hippocampus) and body (temporal muscle) temperature, was used to study intravenous cocaine self-administration in trained rats. The first self-administration of a session was preceded by a strong temperature increase that continued after the drug infusion. ⋯ These data suggest a generalized brain activation associated with cocaine-seeking and cocaine-taking behavior with its phasic fluctuations around individual drug self-injections. While the initial component of brain activation preceding the first lever-press for cocaine is internally determined and closely related to behavioral search, subsequent biphasic fluctuations in neural activity associated with repeated drug intakes appear to be drug-mediated. Cocaine-induced potentiation of monoamine transmission is a possible factor for gradual increases in neural activity that drive cocaine seeking, while a rapid, brain concentration-dependent action on Na(+) transport (local anesthetic action) is the most probable factor determining an abrupt, transient cessation of neural activation associated with cocaine reward.
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Choleratoxin B subunit-binding thick myelinated, A-fibre and unmyelinated, capsaicin-sensitive nociceptive C-fibre primary afferent fibres terminate in a strict topographic and somatotopic manner in the spinal cord dorsal horn. Injection of choleratoxin B subunit-horseradish peroxidase conjugate into injured but not intact peripheral nerves produced transganglionic labelling of primary afferents not only in the deeper layers (Rexed's laminae III-IV), but also in the substantia gelatinosa (Rexed's laminae II) of the spinal dorsal horn. This was interpreted in terms of a sprouting response of the Abeta-myelinated afferents and suggested a contribution to the pathogenesis of neuropathic pain [Nature 355 (1992) 75; J Comp Neurol 360 (1995) 121]. ⋯ In contrast, the proportion of labelled unmyelinated dorsal root axons relating to the transected, but not the intact nerves showed a significant, six-fold increase after sciatic nerve transection (intact: 4.9+/-1.3%; transected: 35+/-6.7%). These observations indicate that peripheral nerve lesion-induced transganglionic labelling of the substantia gelatinosa by choleratoxin B subunit-horseradish peroxidase may be primarily accounted for by the uptake and transganglionic transport of choleragenoid by injured capsaicin-sensitive C-fibre afferents rather than a sprouting response of A-fibre afferents. The present findings suggest an essential role of capsaicin-sensitive primary sensory neurons in lesion-induced spinal neuroplastic changes and provide further support for C-fibre nociceptor neurons being promising targets for the development of new strategies in pain management.
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Remote areas undergoing delayed neuronal degeneration after focal brain ischemia display a preceding glial activation. The expression of proinflammatory cytokines there has not been examined so far. We examined the expression of TNFalpha in the thalamus and the substantia nigra pars reticulata (SNr) 1, 3 and 7 days after transient middle cerebral artery occlusion (MCAO) of the rat. ⋯ Neuronal degeneration was evident at day 14. Thus, in both areas, expression of TNFalpha precedes astrogliosis and neuronal degeneration. The different patterns of TNFalpha upregulation of the substantia nigra pars reticulata and the thalamus following middle cerebral artery occlusion may reflect different pathophysiological mechanisms leading to remote neuronal degeneration.