Neuroscience
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Electrophysiological recordings were used to investigate the effects of ATP analogues on theta-burst-induced long-term potentiation (LTP) in rat hippocampal slices. alpha,beta-Methylene ATP (alpha,beta-MeATP; 20 microM) decreased LTP from 36+/-9% to 17+/-5%, an effect prevented by adenosine A(1) receptor blockade in accordance with the localised catabolism of ATP analogues into adenosine, leading to adenosine A(1) receptor activation. Thus, to probe the role of extracellular ATP, all experiments were performed with the A(1) receptor selective antagonist, 1,3-dipropyl-8-cyclopentylxanthine (50 nM). In these conditions, alpha,beta-MeATP or 5'-adenylylimido-diphosphate (beta,gamma-ImATP; 20 microM) facilitated LTP by 120%, an effect prevented by the P2 receptor antagonists, pyridoxalphosphate-6-azophenyl-2'-4'-disulphonic acid (PPADS; 20 microM) or suramin (75 microM), as well as by the P2X(1/3)-selective antagonist 8-(benzamido)naphthalene-1,3,5-trisulfonate (10 microM). ⋯ Furthermore, beta,gamma-ImATP (20 microM) enhanced [(3)H]adenosine outflow from rat hippocampal slices by nearly 150%, an effect prevented by PPADS (20 microM) or suramin (75 microM). The adenosine transport inhibitors, nitrobenzylthioinosine (5 microM) and dipyridamole (10 microM) also prevented beta,gamma-ImATP (20 microM)-induced [(3)H]adenosine outflow and facilitation of LTP. These results suggest that ATP analogues facilitate LTP through P2 receptor activation that mainly triggers adenosine release leading to the activation of adenosine A(2A) receptors.
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Comparative Study
Gonadal hormones differentially modulate cocaine-induced conditioned place preference in male and female rats.
There is accumulating evidence that suggests there are sex differences in behavioral and subjective responses to cocaine. However, it is not known whether differences in cocaine reward contribute to sex differences in these responses or whether gonadal hormones affect the rewarding properties of cocaine. In the present study, conditioned place preference (CPP), a measure of non-contingent reward, was used to determine the effects of endogenous gonadal hormones and of estrogen and progesterone replacement on cocaine reward. ⋯ While no effects of castration were observed, ovariectomy decreased levels of dopamine and serotonin in the ventral tegmental area. In females, progesterone replacement increased levels of serotonin and dopamine in the ventral tegmental area, while estrogen plus progesterone replacement increased dopamine levels in the nucleus accumbens. Collectively, these results indicate that ovarian hormones may influence cocaine reward by altering monoaminergic systems, which, in turn, may contribute to the current sex disparities in overall cocaine use.
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Comparative Study
Role and regulation of p53 in depolarization-induced neuronal death.
The tumor suppressor gene p53 is a potent transcriptional regulator for genes involved in many cellular activities including cell cycle arrest and apoptosis. In this study, we examined the role of p53 in neuronal death induced by the sodium channel modulator veratridine. We also analyzed the involvement of Ca2+, mitochondria and reactive oxygen species in p53 activation. ⋯ Antisense knockdown of p53 resulted in a significant increase in neuronal survival after veratridine treatment. This protective effect was maintained on N-methyl-D-aspartate or ischemia-induced death but not on staurosporine cytotoxicity. These results together suggest that p53-expression is involved in veratridine-induced neuronal death and that p53 might be a link between toxic stimuli of different types and neuronal death.
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Comparative Study
The role of metabotropic glutamate receptors in regulation of striatal proenkephalin expression: implications for the therapy of Parkinson's disease.
Overactivity of the striatopallidal pathway, associated with an enhancement of enkephalin expression, has been suggested to contribute to the development of parkinsonian symptoms. The aim of the present study was to examine whether the blockade of group I metabotropic glutamate receptors: subtypes 1 and 5 (mGluR1/5), or stimulation of group II: subtypes 2 and 3 (mGluR2/3) may normalize enkephalin expression in the striatopallidal pathway in an animal model of parkinsonism. The proenkephalin mRNA level measured by in situ hybridization in the striatum was increased by pretreatments with haloperidol (1.5 mg/kg s.c., three times, 3 h apart). ⋯ None of the abovementioned antagonists of mGluR1 and mGluR5 per se influenced the proenkephalin expression. Differential effects were induced by agonists of the group II mGluRs, viz. (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine administered intraventricularly (3 times at 0.1-0.2 microg/4 microl, 3 h apart) increased both the normal and haloperidol-increased proenkephalin mRNA level, whereas (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate injected intrastriatally (3 times at 15 microg/0.5 microl, 3 h apart) was ineffective. The present study indicates that the blockade of striatal glutamate receptors belonging to the group I (mGluR1 and mGluR5) but not stimulation of the group II mGluRs may normalize the function of the striatopallidal pathway in an animal model of parkinsonism, which may be important for future antiparkinsonian therapy in humans.
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The viral transneuronal labeling method was used to demonstrate that orexin-containing neurons of the lateral hypothalamic area (LHA) are linked via multisynaptic connections to different sympathetic outflow systems. Two different types of transneuronal tracing experiments were performed: single- and double-virus studies. In the first series of experiments, Bartha pseudorabies virus (PRV), a retrograde transneuronal tracer, was injected into single sympathetic targets, viz., stellate ganglion, adrenal gland, celiac ganglion, and kidney. ⋯ The reverse placement of viral injections was made in another set of rats. In both paradigms, some orexin LHA neurons were transneuronally labeled with both viruses, indicating that they are capable of modulating multiple sympathetic outflow systems. These findings raise the possibility that orexin LHA neurons regulate general sympathetic functions, such as those that occur during arousal or the fight-or-flight response.