Showing papers by "David Fiorella published in 1993"

Effects of chronic cocaine administration on the serotonergic system in the rat brain

Abstract: Male Sprague-Dawley rats received injections of cocaine (20 mg/kg/dose, IP) every 12 h for 14 days and were sacrificed on the 15th day. The chronic cocaine treatment caused an increase in the levels of serotonin [5-hydroxytryptamine (5-HT)] and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the hippocampus. 5-HIAA levels in the frontal cortex were also increased, but 5-HT levels were unaltered by the chronic cocaine treatment. Similarly, striatal levels of 5-HT and 5-HIAA were unchanged by repeated administration of cocaine. Chronic cocaine administration did not alter the density of [3H]8-OH(DPAT), [3H]mesulergine, or [3H]ketanserin binding in the hippocampus, choroid plexus, and frontal cortex, respectively. Furthermore, repeated injection of cocaine did not alter serotonergic-mediated inhibition of adenylate cyclase activity. Thus, repeated administration of cocaine causes region-specific alterations in 5-HT levels but does not change the properties of the 5-HT1A, 5-HT1C, or 5-HT2 receptors.

Role of extracellular adenosine in ethanol-induced desensitization of cyclic AMP production.

Abstract: The decrease in receptor-stimulated cyclic AMP production after chronic ethanol exposure was suggested previously to be secondary to an ethanol-induced increase in extracellular adenosine. The present study was undertaken to ascertain whether a similar mechanism was responsible for the ethanol-induced desensitization of cyclic AMP production in PC12 pheochromocytoma cells. The acute addition of ethanol in vitro significantly increased both basal cyclic AMP content and extracellular levels of adenosine. A 4-day exposure to ethanol decreased basal as well as 2-chloroadenosine- and forskolin-stimulated cyclic AMP contents. No change in cyclic AMP content was observed after a 2-day exposure of PC12 cells to ethanol. Inclusion of adenosine deaminase during the chronic ethanol treatment significantly decreased extracellular levels of adenosine, yet the percentage decrease in 2-chloroadenosine- and forskolin-stimulated cyclic AMP levels after chronic ethanol exposure was not changed by the inclusion of the adenosine deaminase. Similar results were obtained when the chronic treatment was carried out with serum-free defined media. The ethanol-induced desensitization could not be mimicked by chronic exposure of PC12 cells to adenosine analogues. A 24-h exposure of PC12 cells to 2-chloroadenosine resulted in a decrease in the subsequent ability of this adenosine analogue to stimulate cyclic AMP content, but basal and forskolin-stimulated cyclic AMP levels were increased. Similar results were obtained after a 4-day exposure of PC12 cells to 2-chloroadenosine or 5′-N-ethylcarboxamido-adenosine. The present results indicate that the ethanol-induced decrease in receptor-stimulated cyclic AMP content in PC12 cells is not due to an increase in extracellular adenosine.