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These experiments examined the influence of fluoxetine on ethanol-induced conditioned place preference, ethanol-induced conditioned taste aversion, and ethanol discrimination. In the place conditioning experiment, male Swiss-Webster mice received 4 pairings of a distinctive floor cue with 2 g/kg ethanol, 10 mg/kg fluoxetine + ethanol, or fluoxetine alone. A different floor was paired with saline. During conditioning ethanol produced locomotor stimulation. Fluoxetine + ethanol resulted in greater levels of locomotor activity during conditioning trials 2-4. Fluoxetine alone also caused increases in activity. Floor preference testing revealed conditioned place preference in groups receiving ethanol. Fluoxetine did not change the magnitude of ethanol-induced conditioned place preference nor produced place conditioning alone. In the taste conditioning procedure, mice received 1-h access to 0.2 M NaCl solution followed by injections of 0, 5 or 10 mg/kg fluoxetine and 0 or 2.5 g/kg ethanol. Ethanol produced reductions in NaCl intake. Fluoxetine (10 mg/kg) enhanced the development of ethanol-conditioned taste aversion but did not cause taste aversion alone. In the ethanol discrimination experiment, mice were trained to respond for 10% sucrose on an FR20 schedule following injections of either 1 g/kg ethanol or saline. Following acquisition, 10 mg/kg fluoxetine pretreatment enhanced ethanol-appropriate responding at a dose of ethanol (0.5 g/kg) below the training dose. These results indicate enhancement of serotonergic activity influences ethanol aversion and discrimination but not ethanol reward.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9353173&dopt=Abstract
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J Pharmacol Exp Ther. 1997 Nov;283(2):581-91.
In vivo criteria to differentiate monoamine reuptake inhibitors from releasing agents: sibutramine is a reuptake inhibitor.
Gundlah C, Martin KF, Heal DJ, Auerbach SB.
Department of Biological Sciences, Rutgers University, Piscataway, New Jersey 08855, USA.
Because monoamine reuptake inhibitors and releasing agents both increase extracellular neurotransmitter levels, establishing in vivo experimental criteria for their classification has been difficult. Using microdialysis in the hypothalamus of unanesthetized rats, we provide evidence that serotonin- (5-HT) selective and nonselective reuptake inhibitors can be distinguished from the 5-HT-releasing agent fenfluramine by four criteria: 1) Systemic fenfluramine produces a much greater increase in 5-HT than the reuptake inhibitors. 2) The 5-HT somatodendritic autoreceptor agonist, (+/-)-8-hydroxy-(dipropylamino)tetralin (8-OH-DPAT), attenuates the increase in 5-HT produced by reuptake inhibitors, but not by fenfluramine. 3) The large increase in 5-HT produced by infusion of reuptake inhibitors into the hypothalamus is attenuated by their systemic administration. However, systemic injection of fenfluramine during its local infusion does not attenuate this increase. 4) Reuptake inhibitor pretreatment attenuates fenfluramine-induced increases in 5-HT. According to these criteria, the in vivo effects of the novel antiobesity drug sibutramine are consistent with its characterization as a 5-HT reuptake inhibitor and not a 5-HT releaser. Thus, sibutramine produced increases in hypothalamic 5-HT similar in magnitude to the effects of the known reuptake inhibitors, and the increase was attenuated by 8-OH-DPAT. Also, sibutramine attenuated fenfluramine-induced 5-HT release. Systemic administration of sibutramine failed to attenuate the increase in 5-HT produced by its local infusion, suggesting that this criterion is not applicable to compounds with low affinity for the 5-HT transporter.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9353373&dopt=Abstract
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Psychiatr Serv. 1997 Nov;48(11):1420-6.
Effect of antidepressant therapy on health care utilization and costs in primary care.
Croghan TW, Lair TJ, Engelhart L, Crown WE, Copley-Merriman C, Melfi CA, Obenchain RL, Buesching DP.
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
OBJECTIVE: Four groups of patients receiving different antidepressant drugs in a primary care setting were compared in terms of duration of antidepressant therapy and health and mental health care utilization and costs. METHODS: A retrospective analysis of the medical and pharmacy claims of an employed population and their families was conducted. A total of 1,242 patients with a diagnosis of depression were included in the analyses. The four antidepressant cohorts were fluoxetine (N = 799), trazodone (N = 89), the tricyclics amitriptyline and imipramine (N = 104), and the secondary amine tricyclics desipramine and nortriptyline (N = 250). The primary outcome measures were total health care charges, total charges for mental health services, and the pattern of antidepressant use. Secondary measures included charges for outpatient care and pharmacy and the number of outpatient visits. Data analysis involved use of two-stage multivariate regression modeling known as sample selection models. RESULTS: Patients taking fluoxetine achieved higher rates of continuous use for at least six months compared with those taking the other drugs. After selection bias due to observed and unobserved characteristics and other confounding variables was adjusted for, no significant differences were found between drug cohorts in total medical charges. CONCLUSIONS: Improvements in the process of care at no apparent increase in total charges appear possible through appropriate medication therapy.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9355169&dopt=Abstract
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