Fluoxetine Administration Exacerbates Oral Tremor and Striatal Dopamine Depletion in a Rodent Pharmacological Model of Parkinsonism

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
Samantha J PodurgielJohn D Salamone

Abstract

The cardinal motor symptoms of Parkinson's disease (PD) include resting tremor, akinesia, bradykinesia, and rigidity, and these motor abnormalities can be modeled in rodents by administration of the VMAT-2 (type-2 vesicular monoamine transporter) inhibitor tetrabenazine (9,10-dimethoxy-3-(2-methylpropyl)-1,3,4,6,7, 11b hexahydrobenzo[a]quinolizin-2-one; TBZ). Depression is also commonly associated with PD, and clinical data indicate that selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine ((±)-N-methyl-γ-[4-(trifluoromethyl)phenoxy]benzenepropanamine hydrochloride; FLX) are frequently used to treat depression in PD patients. The aim of the present study was to characterize the effect of FLX on the motor dysfunctions induced by a low dose of TBZ (0.75 mg/kg), and investigate the neural mechanisms involved. This low dose of TBZ was selected based on studies with rat models of depressive symptoms. In rats, coadministration of FLX (2.5, 5.0, and 10.0 mg/kg) increased TBZ-induced oral tremor (tremulous jaw movements), and decreased locomotor activity compared with administration of TBZ alone. Coadministration of the serotonin 5-HT2A/2C antagonist mianserin (2.5 and 5.0 mg/kg) attenuated the increase in oral tremor ind...Continue Reading

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Citations

May 30, 2015·Pharmacology, Biochemistry, and Behavior·Samantha E YohnJohn D Salamone
Oct 20, 2015·Behavioural Processes·Benjamin R Eisenreich, Allen Szalda-Petree
Jun 25, 2015·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Samantha E YohnJohn D Salamone
Jul 6, 2016·Frontiers in Behavioral Neuroscience·Lauren L LongJohn D Salamone
Jul 28, 2016·Neuroscience Research·Yasuha IkawaTomio Inoue
Nov 2, 2018·Current Medicinal Chemistry·Kyoung Sang ChoGyun Jee Song
Nov 10, 2017·Movement Disorders : Official Journal of the Movement Disorder Society·Rick C Helmich

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