Serotonin Reuptake Inhibition by Citalopram in Rat Strains Differing for Their Emotionality

Abstract

Acute administration of the selective serotonin (5-HT) reuptake inhibitor (SSRI), citalopram (1-10 mg/kg, i.p

The promiscuity of the dopamine transporter: Implications for the kinetic analysis of [3H]serotonin uptake in rat hippocampal and striatal synaptosomes

“…The apparent disparity between our findings and those of previous studies may also be the result of 5-HT uptake via DAT and SERT; most notably under experimental circumstances in which the contribution of DAT was not inhibited. In striatal synaptosomes incubated without GBR 12909 and using 10 μM fluoxetine to define nonspecific uptake, the K m value that we report is consistent with those reported in previous studies using striatal synaptosomes without DAT inhibition (Martin et al, 2000, Pollier et al, 2000.…”

“…For the kinetic analysis of [ 3 H]5-HT uptake into striatal synaptosomes, in which there is significant DAT expression, four sets of experiments were performed in which synaptosomes were incubated with: (1) fluoxetine to define nonspecific [ 3 H]5-HT uptake and GBR 12909 to inhibit DAT function, (2) fluoxetine to define nonspecific uptake without DAT inhibition, (3) paroxetine to define nonspecific uptake and GBR 12909 to inhibit DAT, or (4) paroxetine to define nonspecific uptake without DAT inhibition. A concentration of 10 μM fluoxetine was selected based on its common use in kinetics studies of 5-HT uptake inhibition (Asano et al, 1997, Martin et al, 2000, Pollier et al, 2000, Zhang et al, 2002, Fernandez et al, 2003. In an effort to achieve selective 5-HT uptake at SERT, a concentration of 0.05 μM paroxetine was selected, which is 200-fold higher than its K i at SERT (0.1 -0.4 nM; for review see Nemeroff & Owens, 2003) and about 20-fold lower than its K i at DAT (1.0 μM; Nemeroff & Owens, 2003;Owens et al, 2001, Koch et al, 2002.…”

“…After the addition of drugs, assay tubes were then incubated at 34°C for 5 min. Following this initial incubation, 50 μl of one of nine 5-HT concentrations (1-300 nM; similar to previous studies; e.g., Martin et al, 2000;Pollier et al, 2000, Fernandez et al, 2003 was added to each tube. For these saturation analyses, the final 5-HT concentration was obtained by adding 20 μl of [ 3 H]5-HT (17 nM) to 30 μl of cold 5-HT (0.225 -4.72 μM).…”

“…Although there is dense serotonergic innervation to rat hippocampus originating in the raphe nuclei, this region is essentially devoid of dopaminergic innervation (Fuxe et al, 1985, Donnan et al, 1989, Mennicken et al, 1992. Although numerous studies have investigated the kinetics of 5-HT re-uptake under varying environmental and pharmacological conditions (O'Reilly and Reith, 1988, Asano et al, 1997, Kokoshka et al, 1998, Wells et al, 1999, Martin et al, 2000, Pollier et al, 2000, Nandi et al, 2004, Nightingale et al, 2005 and in varying rat strains (Martin et al, 2000, Fernandez et al, 2001, Fernandez et al, 2003, few studies have considered the impact of the expression of both DAT and SERT in brain regions such as striatum and the potential contribution of DAT to the analysis of 5-HT uptake kinetics. The heterogeneous expression of DAT and SERT in specific brain regions is also an important factor with regard to selecting specific transporter inhibitors and concentrations to define nonspecific uptake.…”

Effects of clomipramine on self-control choice in Lewis and Fischer 344 rats

“…However, many variations have been noted. For instance, Lewis rats have shown lower levels of 5-HT in the nucleus accumbens (Selim and Bradberry, 1996), but a 3-4 fold higher baseline level of extracellular 5-HT in the hippocampus (Pollier et al, 2000) and significantly fewer 5-HT 1A binding sites in the hippocampus and frontal cortex (Burnet et al, 1996) than Fischer 344 rats. With regard to DA, Lewis rats have shown lower concentrations in the dorsal striatum (Lindley et al, 1999), but there are mixed findings in the nucleus accumbens.…”