Efficacy of paroxetine for the treatment of depression in the context of HIV infection. Drosophila serotonin transporters have voltage-dependent uptake coupled to a serotonin-gated ion channel. A new method of preparing human whole brain sections for in vitro receptor autoradiography. Rx drugs

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Pharmacopsychiatry. 1997 Mar;30(2):70-1.
Efficacy of paroxetine for the treatment of depression in the context of HIV infection.

Grassi B, Gambini O, Garghentini G, Lazzarin A, Scarone S.

Department of Neuropsychiatric Sciences, University of Milan Medical School, Italy.

Recent studies in the literature point out that HIV-infected subjects are affected by depression with a relatively high frequency. The aim of this study was to assess the efficacy and tolerability of paroxetine for the treatment of depression in the context of HIV infection. 15 HIV-infected subjects (10 patients with a major depressive episode and 5 patients with an adjustment disorder with depressed mood, according to the DSM IV diagnostic criteria) were administered paroxetine at a daily dosage of 20 mg. Depressive symptomatology was monitored by means of the Hamilton Rating Scale for Depression (HAM-D) at the time of enrollment and 2 weeks, 4 weeks, and 6 weeks later; at the same times adverse effects were recorded. 14 patients completed the study, and all of these recovered from depression; HAM-D mean scores significantly improved from baseline to final assessment, both when all subjects were considered (ANOVA for repeated measurements: p < or = 0.0001) and when only patients with a major depressive episode were included in the statistical analysis (ANOVA for repeated measurements: p < 0.0001). No significant adverse effects were recorded. Because of its efficacy and good tolerability paroxetine seems to be suitable for the treatment of depression in the context of HIV infection.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9131727&dopt=Abstract

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J Neurosci. 1997 May 15;17(10):3401-11.
Drosophila serotonin transporters have voltage-dependent uptake coupled to a serotonin-gated ion channel.

Galli A, Petersen CI, deBlaquiere M, Blakely RD, DeFelice LJ.

Center for Molecular Neuroscience, Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-6600, USA.

Serotonin (5HT) transporters (SERTs) couple to existing ion gradients to transport 5HT into presynaptic terminals. In mammalian SERTs, the transport cycle is reported as electroneutral, with a translocation of zero net charge, and 5HT uptake is independent of membrane voltage. Yet mammalian SERTs exhibit 5HT-induced currents, and Drosophila SERTs (dSERTs) show voltage-dependent uptake. Thus, the relationship between uptake and current remains controversial; furthermore, the number of 5HT molecules translocated per ion channel event is unknown. To investigate this, we have used heterologous expression of cloned dSERTs to measure 5HT flux and dSERT currents concurrently under voltage clamp, and we have used fluctuation analysis to measure the size of the elementary ionic events in the same cells. RNA-injected Xenopus oocytes accumulate 5HT, and paroxetine or desipramine inhibit this uptake. RNA-injected oocytes also display paroxetine-sensitive 5HT-induced currents and 5HT-independent leak currents. Na replacement decreases the uptake and the induced currents. 5HT-induced current and 5HT uptake both increase at negative potentials, where 5HT carries approximately 5% of the induced current. Recently, several groups have reported similar phenomena for other transporters, in which transmitter-induced currents exceed the predictions of coupled transport. We now provide evidence that in dSERT, approximately 500 5HT molecules are translocated per channel opening, which, at -20 mV, carries approximately 10,000 electronic charges. These data support a model in which 500 SERT cycles occur for each 5HT-induced channel opening or a model in which 500 5HT molecules and 10,000 electronic charges pass through a common pore.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9133366&dopt=Abstract

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J Neurosci Methods. 1997 Apr 4;72(2):147-51.
A new method of preparing human whole brain sections for in vitro receptor autoradiography.

Miller JK, Bowery NG, Tulloch IF.

The School of Pharmacy, London University, UK.

In vitro receptor autoradiography is a widely used technique for determining the distribution of radioligand binding sites. By using this technique it is possible to investigate alterations in receptor number and affinity caused by trauma or a disease state. To date, however, the largest sections prepared for in vitro autoradiography have been from single human hemispheres, with the adjacent hemisphere being used for neuropathological investigations. Therefore, a method for cutting large cryosections of human whole brain tissue is described. Whole brains obtained less than 2 days postmortem were frozen at -80 degrees C. 1.5-2 cm coronal slices were cut from the brain and embedded and frozen in a carboxymethylcellulose solution. Sections 40 microm in size were sliced from the frozen block at -16 degrees C in a whole body cryostat. The sections were lifted by means of a nylon membrane backing material and subsequently incubated with tritiated ligand to produce autoradiograms of each whole brain coronal section. [(3)H]paroxetine was used in the present study as an example.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9133578&dopt=Abstract

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