Neuroscience
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Adenosine A(1) receptors are inhibitory G-protein coupled receptors that presynaptically regulate neurotransmitter release, but their role in self-regulating adenosine release is not known. In this study, we examined the modulation of evoked adenosine and dopamine efflux by A(1) receptors and studied whether D(1) receptors mediate these effects. Fast-scan cyclic voltammetry at carbon-fiber microelectrodes was used for the simultaneous detection of adenosine and dopamine efflux on a subsecond time scale. ⋯ Thus, A(1) and D(1) receptors have a synergistic interaction that modulates both stimulated adenosine and dopamine. The decrease in adenosine is not a downstream effect of lowered dopamine release, as decreasing dopamine synthesis and release with α-methyl-p-tyrosine or increasing release with haloperidol had no effect on adenosine release. This study shows that A(1) receptors have some characteristics of an autoreceptor, including self-regulation of adenosine release.
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Environmental enrichment (EE) introduced during abstinence from cocaine self-administration is protective in reducing cue-elicited incentive motivation for cocaine in rats. This study examined neural activation associated with this protective effect of EE using Fos protein expression as a marker. Rats were trained to press a lever reinforced by cocaine (0.75 mg/kg/0.1 mL infusion) and light and tone cues across 15 consecutive days during which they were all housed in isolated conditions (IC). ⋯ In contrast, IC enhanced Fos expression in the dorsal caudate putamen, substantia nigra, and central amygdala, evident as an increase relative to both PC and EE. These results suggest that EE blunts neural activation throughout the mesocorticolimbic circuitry involved in cue-elicited incentive motivation for cocaine, whereas IC enhances activation primarily within the nigrostriatal dopamine pathway. These findings have important implications for understanding and treating drug-conditioned craving in humans.
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Comparative Study
Glutamate transporter type 3 knockout mice have a decreased isoflurane requirement to induce loss of righting reflex.
Excitatory amino acid transporters (EAAT) uptake extracellular glutamate, the major excitatory neurotransmitter in the brain. EAAT type 3 (EAAT3), the main neuronal EAAT, is expressed widely in the CNS. We have shown that the volatile anesthetic isoflurane increases EAAT3 activity and trafficking to the plasma membrane. ⋯ Interestingly, the EAAT3 knockout mice did not have an altered sensitivity to the hypnotic effects caused by ketamine, an i.v. anesthetic that is a glutamate receptor antagonist and does not affect EAAT3 activity. These results suggest that EAAT3 modulates the sensitivity of neural circuits to isoflurane. These results, along with our previous findings which suggests that isoflurane increases EAAT3 activity, indicate that EAAT3 may regulate isoflurane-induced behavioral changes, including anesthesia.
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Comparative Study
Distinct effects of sonic hedgehog and Wnt-7a on differentiation of neonatal neural stem/progenitor cells in vitro.
Sonic hedgehog (Shh) and Wnt-7a are morphogens involved in embryonic as well as ongoing adult neurogenesis. Their effects on the differentiation and membrane properties of neonatal neural stem/progenitor cells (NS/PCs) were studied in vitro using NS/PCs transduced with either Shh or Wnt-7a. Eight days after the onset of in vitro differentiation the cells were analyzed for the expression of neuronal and glial markers using immunocytochemical and Western blot analysis, and their membrane properties were characterized using the patch-clamp technique. ⋯ The electrophysiological analysis revealed that Wnt-7a increased, while Shh decreased the incidence of cells displaying a neuron-like current pattern, represented by outwardly rectifying K(+) currents and tetrodotoxin-sensitive Na(+) currents. Additionally, Wnt-7a increased cell proliferation only at the early stages of differentiation, while Shh promoted proliferation within the entire course of differentiation. Thus we can conclude that Shh and Wnt-7a interfere differently with the process of neuronal differentiation and that they promote distinct stages of neuronal differentiation in neonatal NS/PCs.
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A significant number of postmenopausal women report increased anxiety and vulnerability to stress, which has been linked to decreased secretion of ovarian steroids. Communication between the serotonin system and the corticotropin releasing factor (CRF) system determines stress sensitivity or resilience. This study examines the effects of the ovarian steroids, estradiol (E) and progesterone (P) on the CRF system components that impact serotonin neurons in the midbrain of nonhuman primates. ⋯ E±P increased UCN1 immunostaining in the cell bodies and increased UCN1 fiber density in the caudal linear nucleus. Estrogen receptor beta (ERβ), but not ERα was detected in the nucleus of UCN1-positive neurons. While the mechanism of ovarian hormone regulation of the midbrain CRF system requires further investigation, these studies clearly demonstrate another pathway by which ovarian hormones may have positive effects on anxiety and mood regulation.