ISSN:0955-8810    

出版商:OVID    

年代:1996

数据来源: OVID

ISSN:0955-8810    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The rapidly advancing technology in the area of molecular neuroscience has greatly expanded the tools available to behavioural pharmacologists for investigating the molecular bases underlying the interrelation of pharmacological agents and behaviour. Strategies such as gene targeted knockout mutations, expression of an exogenous transgene, as well as the disruption of the cellular expression of genes with antisense oligonucleotides, are being successfully used to study normal and impaired behavioural function. Advantages of these genetic methods include the ability to manipulate systems for which selective pharmacological ligands do not exist, and the opportunity to study the interaction between genotype and environment without having to rely on spontaneously occurring mutants or selective breeding programmes. By targeting particular genes, questions can be asked about how genes control neuronal function and how manipulations of these genes affect behaviour. In particular, these strategies have been applied to studies of the molecular bases for disrupted behaviours, the behavioural actions of psychoactive drugs, and models of neuropsychiatric and neuropathological disorders. These emerging molecular biological techniques complement traditional pharmacological analysis to provide a very powerful approach with which to study the molecular correlates of behavioural pharmacology.

ISSN:0955-8810    

出版商:OVID    

年代:1996

数据来源: OVID

ISSN:0955-8810    

出版商:OVID    

年代:1996

数据来源: OVID

ISSN:0955-8810    

出版商:OVID    

年代:1996

数据来源: OVID

ISSN:0955-8810    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Consequent to the insertion of the human Cu/Zn-superoxide dismutase (SOD) transgene, SOD transgenic mice (SOD-Tg) show higher concentrations of the primary receptor thought to be involved in opioid reinforcement (μ). These increases are observed in areas specifically associated with the primary neurotransmitter thought to be involved in addiction (dopamine), and in neuroanatomical regions thought to mediate substance abuse (mesolimbic). In the present study we have tested the idea that these increases in μ-receptors are associated with parallel changes in μ-mediated behaviors. Baseline and morphine-induced locomotor activity were significantly altered in the SOD-Tg mice. A qualitative change in the nature of acute and chronic morphine-induced locomotor activity was demonstrated by a significant change in the slope of the dose-effect curve. SOD-Tg mice were significantly more sensitive to the locomotor stimulant effects of morphine. Intravenous morphine-reinforced behavior was also altered in the SOD-Tg mice. SOD-Tg mice showed significant dose-related changes in operant lever-press responding maintained by morphine injection and significantly greater amounts of behavior were maintained by the drug than by vehicle under an intermittent schedule of reinforcement. In addition, SOD-Tg mice increased operant responding for the drug when the amount of behavior required to maintain drug intake increased 10-fold under a PR schedule of reinforcement. In contrast, in wild-type mice morphine injections failed to maintain greater amounts of behavior than vehicle, there were no dose-related changes in behavior, and when response requirements increased under the PR schedule, morphine intake decreased significantly. Thus, SOD transgene insertion significantly enhanced the efficacy of morphine as a reinforcer.

ISSN:0955-8810    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Although microdialysis is commonly understood as a method of sampling low molecular weight compounds in the extracellular compartment of tissues, this definition appears insufficient to specifically describe brain microdialysis of neurotransmitters. In fact, transmitter overflow from the brain into dialysates is critically dependent upon the composition of the perfusing Ringer. Therefore, the dialysing Ringer not only recovers the transmitter from the extracellular brain fluid but is a main determinant of its in-vivo release. Two types of brain microdialysis are distinguished: quantitative microdialysis and conventional microdialysis. Quantitative microdialysis provides an estimate of neurotransmitter concentrations in the extracellular fluid in contact with the probe. However, this information might poorly reflect the kinetics of neurotransmitter releasein vivo. Conventional microdialysis involves perfusion at a constant rate with a transmitter-free Ringer, resulting in the formation of a steep neurotransmitter concentration gradient extending from the Ringer into the extracellular fluid. This artificial gradient might be critical for the ability of conventional microdialysis to detect and resolve phasic changes in neurotransmitter release taking place in the implanted area. On the basis of these characteristics, conventional microdialysis of neurotransmitters can be conceptualized as a model of the in-vivo release of neurotransmitters in the brain. As such, the criteria of face-validity, construct-validity and predictive-validity should be applied to select the most appropriate experimental conditions for estimating neurotransmitter release in specific brain areas in relation to behaviour.

ISSN:0955-8810    

出版商:OVID    

年代:1996

数据来源: OVID

ISSN:0955-8810    

出版商:OVID    

年代:1996

数据来源: OVID

ISSN:0955-8810    

出版商:OVID    

年代:1996

数据来源: OVID