Prozac (fluoxetine, lilly 110140), the first selective serotonin uptake inhibitor and an antidepressant drug: Twenty years since its first publication

Wong, David T.; Bymaster, Frank P.; Engleman, Eric A.

doi:10.1016/0024-3205(95)00209-o

Cited by 594 publications

(422 citation statements)

References 221 publications

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“…Alternatively, reduced fluid intake may have resulted from a conditioned taste aversion produced by fluoxetine (Prendergast et al, 1996). Fluoxetine-treated rats also gained significantly less weight than controls, an effect that is consistent with other animal Caccia et al, 1997;Durand et al, 1999) and human studies (Wong et al, 1995).…”

Section: Acute Drug Effectssupporting

confidence: 77%

“…The mainstay for treatment of anxiety and depression are specific serotonin re-uptake inhibitor (SSRI) drugs such as fluoxetine (Prozac) (Vaswani et al, 2003;Wong et al, 1995). However, if MDMA permanently damages 5-HT neurons, it is uncertain whether SSRI drugs will have efficacy in treating MDMA users, even after periods of abstinence from MDMA.…”

Section: Introductionmentioning

confidence: 99%

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Chronic Fluoxetine Treatment Partly Attenuates the Long-Term Anxiety and Depressive Symptoms Induced by MDMA (‘Ecstasy’) in Rats

Thompson

Clemens

et al. 2003

Neuropsychopharmacol

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Use of the drug 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy') can have long-term adverse effects on emotion in both humans and laboratory animals. The present study examined whether chronic treatment with the antidepressant drug fluoxetine could reverse such effects. Male Wistar rats were briefly exposed to MDMA (4 Â 5 mg/kg over 4 h) or vehicle on 2 consecutive days. Approximately 9-12 weeks later, half of the rats received a dose of approximately 6 mg/kg/day fluoxetine in their drinking water for a 5-week period. Fluoxetine administration reduced fluid intake and body weight in MDMA and vehicle pretreated rats. After several weeks of fluoxetine treatment, rats were assessed on the social interaction test, the emergence test of anxiety and the forced swim model of depression. MDMA pretreated rats showed reduced social interaction, increased anxiety on the emergence test, and increased immobility and decreased active responses in the forced swim test. Fluoxetine treatment reversed MDMA-induced anxiety in the emergence test and depressive-like effects in the forced swim test, yet exhibited no effects on the social interaction test. MDMA pretreated rats had decreased 5-HT and 5-HIAA levels in limbic and cortical regions, and decreased density of serotonin transporter sites in the cortex. Fluoxetine treatment did not greatly affect 5-HT levels in MDMA pretreated rats, but significantly decreased 5-HIAA levels in all brain sites examined. Postmortem blood serum levels of fluoxetine and norfluoxetine did not differ in MDMA and vehicle pretreated rats. These results indicate that fluoxetine may provide a treatment option for some of the deleterious long-term effects resulting from MDMA exposure.

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Section: Acute Drug Effectssupporting

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Chronic Fluoxetine Treatment Partly Attenuates the Long-Term Anxiety and Depressive Symptoms Induced by MDMA (‘Ecstasy’) in Rats

Thompson

Clemens

et al. 2003

Neuropsychopharmacol

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“…These actions may be important towards determining the etiology and treatment of mental depression, because zinc and fluoxetine, 28,34 as well as the nicotinic receptor system, 2,35 have been implicated in the disease.…”

Section: Discussionmentioning

confidence: 99%

Combined actions of zinc and fluoxetine on nicotinic acetylcholine receptors

2004

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Zinc and nicotinic acetylcholine receptors (nAChRs) seem to be associated with major depression, and some antidepressants, including fluoxetine (Prozac), antagonize nAChRs. Therefore, a study was made of the modulation of neuronal a4b4 and muscle a1b1gd nAChRs, expressing in oocytes, by the combined action of zinc and fluoxetine. At a holding potential of -60 mV, 200 mM zinc increased by 361% the currents elicited by acetylcholine (ACh currents) for a4b4 and by 182% for a1b1gd nAChRs. In contrast, 5 mM fluoxetine reduced the ACh currents to 31% for a4b4 and to 45% for a1b1gd nAChRs. Additionally, fluoxetine reduced more the ACh currents in the presence of zinc: to 17% for a4b4 and to 19% for a1b1gd nAChRs, and after washing out the fluoxetine the ACh current did not recover its zinc-potentiated value. Moreover, when ACh-activated nAChRs were exposed first to fluoxetine and then zinc was added, the potentiating effect of zinc was very small for muscle nAChRs and was nil for neuronal receptors. Thus, the inhibiting effect of fluoxetine prevails over the potentiating action of zinc. Finally, the effects of both zinc and fluoxetine were voltage independent, indicating that these substances interact outside the ion channel. As fluoxetine nullifies the effects of zinc, it appears that both substances interact in the same site. These results should help understand better the roles played by zinc, antidepressants, nAChRs and their combination in brain functions and in the treatment of depression.

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“…The purpose of the present study was to test the hypothesis that reduced serotonergic neurotransmission mediates some of the affective aspects, not only of non-drug-induced depressions, but also of druginduced depressions. Thus, the present study tested the hypothesis that enhancement of serotonergic neurotransmission through acute administration of the selective serotonin reuptake inhibitor (SSRI) fluoxetine (Wong et al 1995) in combination with a relatively selective 5-HT 1A receptor antagonist would alleviate the symptom of "diminished interest or pleasure" observed in rats during nicotine or amphetamine withdrawal. Such an experimental outcome would suggest that the affective aspects of drug withdrawal may be homologous to the core symptom of depression of "diminished interest or pleasure" in rewarding stimuli.…”

mentioning

confidence: 99%

Fluoxetine Combined with a Serotonin-1A Receptor Antagonist Reversed Reward Deficits Observed during Nicotine and Amphetamine Withdrawal in Rats

Harrison

Liem

Markou

2001

Neuropsychopharmacology

158

126

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Cessation of chronic nicotine or amphetamine administration precipitates withdrawal syndromes characterized by affective symptoms, including "diminished interest or pleasure" in rewarding stimuli (i.e., anhedonia) (American Psychiatric Association 1994;Covey et al. 1998;Glassman 1993;Hughes 1992). Interestingly, the symptom of "diminished interest or pleasure" is not only a symptom of drug withdrawal, but also a core symptom of depression and a negative symptom of schizophrenia (American Psychiatric Association 1994;Markou et al. 1998). Brain reward threshold elevation is an operational measure of this symptom because it reflects diminished sensitivity to rewarding electrical stimuli. In rats, withdrawal from drugs of abuse belonging to diverse pharmacological classes, such as nicotine (Epping-Jordan et al. 1998 Watkins et al. 2000b), amphetamine Zacharko 1980a, 1980b;Kokkinidis et al. 1980Kokkinidis et al. , 1986 Barrett 1976, 1980;Lin et al. 1999Lin et al. , 2000Paterson et al. 2000;Wise and Munn 1995), cocaine (Baldo et al. 1999;Kokkinidis and McCarter 1990; Koob 1991, 1992a;Markou et al. 1992) morphine (Schulteis et al. 1994) and ethanol (Schulteis et al. 1995) elevated brain stimulation reward thresholds.In addition to the affective aspects of drug withdrawal reflected in threshold elevations, nicotine, opiate, or ethanol withdrawal also lead to alterations in a set of behaviors termed somatic signs. In the case of nicotine, these somatic signs are primarily gasps, writhes, eye blinks, and ptosis (Epping-Jordan et al. 1998;Hildebrand et al. 1997Hildebrand et al. , 1999Malin et al. 1992). It is unlikely that these somatic signs in the rat reflect the affective component of drug withdrawal. Nevertheless, the study of both threshold elevations and somatic signs permits the investigation of the effects of manipulations on the various aspects of withdrawal.Based on evidence demonstrating the efficacy of serotonergic antidepressant treatments, reduced cerebrospinal fluid levels of serotonin metabolites, endocrine measures reflecting reduced serotonergic neurotransmission and the exacerbation of depressive symptomatology seen after serotonin (5-HT) depletion in depressed individuals, it is hypothesized that reduced serotonergic neurotransmission underlies at least some aspects or some subtypes of non-drug-induced depressions (for reviews, see Caldecott-Hazard et al. 1991; CaldecottHazard and Schneider 1992;Heninger et al. 1996;Markou et al. 1998;Meltzer and Lowy 1988;Willner 1985). The purpose of the present study was to test the hypothesis that reduced serotonergic neurotransmission mediates some of the affective aspects, not only of non-drug-induced depressions, but also of druginduced depressions. Thus, the present study tested the hypothesis that enhancement of serotonergic neurotransmission through acute administration of the selective serotonin reuptake inhibitor (SSRI) fluoxetine (Wong et al. 1995) in combination with a relatively selective 5-HT 1A receptor antagonist would alleviate the symptom of "dimin...

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Prozac (fluoxetine, lilly 110140), the first selective serotonin uptake inhibitor and an antidepressant drug: Twenty years since its first publication

Cited by 594 publications

References 221 publications

Chronic Fluoxetine Treatment Partly Attenuates the Long-Term Anxiety and Depressive Symptoms Induced by MDMA (‘Ecstasy’) in Rats

Chronic Fluoxetine Treatment Partly Attenuates the Long-Term Anxiety and Depressive Symptoms Induced by MDMA (‘Ecstasy’) in Rats

Combined actions of zinc and fluoxetine on nicotinic acetylcholine receptors

Fluoxetine Combined with a Serotonin-1A Receptor Antagonist Reversed Reward Deficits Observed during Nicotine and Amphetamine Withdrawal in Rats

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