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R Revay

Publications and source records attributed to R Revay.

4 recordsLinked to original sources

Cocaine reward models: conditioned place preference can be established in dopamine- and in serotonin-transporter knockout mice.

Cocaine and methylphenidate block uptake by neuronal plasma membrane transporters for dopamine, serotonin, and norepinephrine. Cocaine also blocks voltage-gated sodium channels, a property not shared by methylphenidate. Several lines of evidence have suggested that cocaine blockade of the dopamine transporter (DAT), perhaps with additional contributions from serotonin transporter (5-HTT) recognition, was key to its rewarding actions. We now report that knockout mice without DAT and mice without 5-HTT establish cocaine-conditioned place preferences. Each strain displays cocaine-conditioned place preference in this major mouse model for assessing drug reward, while methylphenidate-conditioned place preference is also maintained in DAT knockout mice. These results have substantial implications for understanding cocaine actions and for strategies to produce anticocaine medications.

Animals↗

Dopamine transporter immunohistochemistry in median eminence, amygdala, and other areas of the rat brain.

In an extension of our previous work, an antibody directed against a peptide from the N-terminal region of DAT was used to localize specific dopamine transporter immunoreactivity (DAT-IR) in several regions of rat brain. Apparent axons and varicosities were found in the zona incerta, external layer of the median eminence, various nuclei of the amygdala, the cortex-amygdala transition zone, and in periglomerular regions in the olfactory bulb. Apparent stained neuronal perikarya and dendrites were observed in the arcuate nucleus and olfactory bulb. These regions are known to have dopaminergic neurons and innervations, although there was not a perfect correspondence between DAT-IR and the known distribution of dopaminergic neurons. A possible explanation is that different dopamine containing cell groups express different levels of DAT mRNA and protein, as we have previously shown. Also in the tuberoinfundibular neurons, for example, DAT-IR was preferentially localized to distal axons in the median eminence, suggesting intracellular compartmentation.

Amygdala↗

Dopamine transporter immunoreactivity in rat brain.

The dopamine transporter (DAT) is a primary site for the action of cocaine in inducing euphoria. Its action is necessary for the selectivities of dopaminergic neurotoxins that provide the best current experimental models of Parkinson's disease. In the present report, rat dopamine transporter-like immunoreactivity (iDAT) was assessed by immunohistochemistry using newly developed polyclonal antisera raised against conjugated peptides corresponding to sequences found in the dopamine transporter's carboxy- and amino-termini. Dense iDAT was observed in patterns consistent with neural processes and terminals in the striatum, nucleus accumbens, olfactory tubercle, nigrostriatal bundle, and lateral habenula. Perikarya in the substantia nigra pars compacta were immunostained with moderate intensity using one of two immunohistochemical methods, while scattered ventral tegmental area perikarya were stained with somewhat less intensity. Immunoreactive neuronal processes with axonal and dendritic morphologies were stained in the substantia nigra and the paranigral and parabrachialis pigmentosus nuclei of the ventral tegmental area, while sparser processes were noted more medially in the ventral tegmental area. Neuronal processes were found in several laminae in the cingulate cortex, with notable fiber densities in the superficial aspects of lamina I and laminae II/III. The intensities of immunoreactivities in striatum and cerebral cortex were dramatically attenuated ipsilateral to nigrostriatal bundle 6-hydroxydopamine lesions. Specificity of immunostaining was supported by agreement of the results using sera directed against two distinct DAT segments, studies with preimmune and preadsorbed sera and studies of the extracted protein. These antisera identify and reveal details of the distribution of DAT immunoreactivity in rat brain and display variations in levels of DAT expression of likely functional significance.

Amino Acid Sequence↗