citalopram escitalopram Lexapro
Effects of chronic treatment with escitalopram or citalopram on extracellular 5-HT in the prefrontal cortex of rats: role of 5-HT1A receptors.

Ceglia I, Acconcia S, Fracasso C, Colovic M, Caccia S, Invernizzi RW.

Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri, Via Eritrea 62, 20157 Milano, Italy.

1 Microdialysis was used to study the acute and chronic effects of escitalopram (S-citalopram; ESCIT) and chronic citalopram (CIT), together with the 5-HT1A receptor antagonist WAY100,635 (N-[2-[methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane carboxamide trihydrochloride) and the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), on extracellular 5-hydroxytryptamine (5-HT) levels in the rat prefrontal cortex. 2 Extracellular 5-HT rose to 234 and 298% of basal values after subcutaneous (s.c.) acute doses of 0.15 and 0.63 mg kg(-1) ESCIT. No further increase was observed at 2.5 mg kg(-1) ESCIT (290%). 3 The effect of 13-day s.c. infusion of 10 mg kg(-1) day(-1) ESCIT on extracellular 5-HT (422% of baseline) was greater than after 2 days (257% of baseline), whereas exposure to ESCIT was similar. In contrast, the increase in extracellular 5-HT induced by the infusion of CIT for 2 (306%) and 13 days (302%) was similar. However, brain and plasma levels of S-citalopram in rats infused with CIT for 13 days were lower than after 2 days. 4 Acute treatment with 2.5 mg kg(-1) ESCIT or 5 mg kg(-1) CIT raised extracellular 5-HT by 243 and 276%, respectively, in rats given chronic vehicle but had no effect in rats given ESCIT (10 mg kg(-1) day(-1)) or CIT (20 mg kg(-1) day(-1)) for 2 or 13 days, suggesting that the infused doses had maximally increased extracellular 5-HT. WAY100,635 (0.1 mg kg(-1) s.c.) increased extracellular 5-HT levels by 168, 174 and 169% of prechallenge values in rats infused with vehicle or ESCIT for 2 or 13 days, respectively. WAY100,635 enhanced extracellular 5-HT levels to 226, 153 and 164% of prechallenge values in rats infused with vehicle or CIT for 2 and 13 days, respectively. 5 8-OH-DPAT (0.025 mg kg(-1)) reduced extracellular 5-HT by 54% in control rats, but had no effect in those given ESCIT and CIT for 13 days. 6 This series of experiments led to the conclusion that chronic treatment with ESCIT desensitizes the 5-HT1A receptors, regulating the release of 5-HT in the prefrontal cortex and enhances the effect of the drug on extracellular 5-HT. They also indicate that chronic treatment with ESCIT and CIT did not prevent WAY100,635 from raising extracellular 5-HT.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15148253&dopt=Abstract citalopram escitalopram Lexapro



citalopram escitalopram Lexapro
Increased responsiveness of presumed 5-HT cells to citalopram in adult rats subjected to prolonged maternal separation relative to brief separation.

Arborelius L, Hawks BW, Owens MJ, Plotsky PM, Nemeroff CB.

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA. lotta.arborelius fyfa.ki.se

RATIONALE: Certain adverse events in childhood, such as loss of a parent or sexual abuse, are associated with an increased vulnerability to develop depression later in life. Prolonged, daily maternal separation of rat pups induces several behavioral, endocrine and neurochemical changes similar to those observed in human depression. OBJECTIVES: Because dysfunction of brain serotonergic systems has been implicated in the pathophysiology of depression, the effects of neonatal maternal separation on these systems was studied in adult rats. METHODS: Male rat pups were subjected to daily maternal separation for 180 min (HMS180) from postnatal day 2 to day 14. Neonatal handled rats, i.e., pups undergoing daily 15-min separations during the same time period (HMS15), were chosen as a control group, since the 180-min separations involved handling of the pups, i.e., the pups were removed from the home cage during the separations. As adults, the effect of citalopram (0.05-0.80 mg/kg, intravenous) on the firing rate of 5-HT neurons in the dorsal raphe nucleus (DRN) was studied. RESULTS: The inhibitory effect of citalopram on serotonergic cell firing was significantly enhanced at doses of 0.1 mg/kg and 0.4 mg/kg in the HMS180 compared with that in the HMS15 rats. However, the number of binding sites and mRNA expression of the 5-HT transporter and 5-HT(1A) receptors in the DRN did not differ between the two rearing groups. CONCLUSION: These findings suggest that early life stress gives rise to persistent changes in the function, but not the density or mRNA expression of central 5-HT(1A) receptors and/or 5-HT transporters.

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citalopram escitalopram Lexapro
Effects of citalopram on the excitability of the human motor cortex: a paired magnetic stimulation study.

Robol E, Fiaschi A, Manganotti P.

Dipartimento di Scienze Neurologiche e della Visione, Sezione Neurologia Riabilitativa, Policlinico Giambattista Rossi, Universita di Verona, Via delle Menegone, 10-Verona 37134, Italy. elisarobol interfree.it

Several recent reports suggest the possibility of monitoring pharmacological effects on brain excitability through transcranial magnetic stimulation (TMS). Different drugs have been studied using paired magnetic stimulation in normal subjects and patients. In particular, it has been suggested that antidepressant drugs may have an appreciable effect on motor excitability. The aim of the present study was to investigate motor area excitability in normal subjects after oral administration of a single dose of citalopram, a selective serotonin reuptake inhibitor (SSRI) antidepressant. Motor cortex excitability was studied by single and paired transcranial magnetic stimulation before and 2.5 and 36 (t1/2=36 h) h after oral administration of 30 mg of citalopram. Cortical excitability was measured using different transcranial magnetic stimulation parameters: motor threshold (MT), motor-evoked potential (MEP) amplitude and latency, motor recruitment, duration of cortical silent period (CSP), intracortical inhibition and intracortical facilitation. Spinal excitability and peripheral nerve conduction were measured by F response and M wave. Temporary but significant increases in motor threshold, motor-evoked potentials, silent period and intracortical inhibition were observed 2.5 h after drug administration, without any significant changes in motor-evoked potential amplitude and latency and spinal excitability parameters. Our findings suggest that a single oral dose of citalopram can induce significant but transitory suppression of motor cortex excitability in normal subjects.

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citalopram escitalopram Lexapro
Antidepressant effects of citalopram and CRF receptor antagonist CP-154,526 in a rat model of depression.

Overstreet DH, Keeney A, Hogg S.

Center for Alcohol Studies, CB #7178, 3009 Thurston-Bowles Building, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7178, USA. dhover med.unc.edu

Due to the interest in the antidepressant potential of nonpeptide corticotropin-releasing factor (CRF)(1) receptor antagonists, the present investigation examined the antidepressant-like effects of the CRF(1) receptor antagonist CP-154,526 on the exaggerated swim test immobility in the Flinders Sensitive Line (FSL) rat, a genetic animal model of depression. Chronic treatment with CP-154,526 (10 mg/kg; 2x day) for 14 days increased swimming in the Flinders Sensitive Line rats. Citalopram (5 and 10 mg/kg; 2x day) and desipramine (5 mg/kg; 1x day) also significantly increased swimming in the Flinders Sensitive Line rats, as expected. However, neither CP-154,526 nor citalopram (10 mg/kg) altered swimming times in the control Flinders Resistant Line (FRL) rats. Citalopram (10 mg/kg) and CP-154,526 also increased the abnormally low level of social interaction behavior in the Flinders Sensitive Line rats. These findings indicate that citalopram and CP154,526, a CRF(1) receptor antagonist, have both antidepressant and anxiolytic effects that can be detected in an experimental model of depression only and not in "normal" control animals.

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citalopram escitalopram Lexapro
Four days of citalopram increase suppression of cortisol secretion by prednisolone in healthy volunteers.

Pariante CM, Papadopoulos AS, Poon L, Cleare AJ, Checkley SA, English J, Kerwin RW, Lightman S.

Division of Psychological Medicine, Institute of Psychiatry, King's College London, 1 Windsor Walk, Denmark Hill, PO 51, London, SE5 8AF, UK. spjucmp iop.kcl.ac.uk

RATIONALE: Chronic antidepressant treatment increases glucocorticoid-mediated negative feedback on the hypothalamic-pituitary-adrenal (HPA) axis, and thus reduces HPA axis activity, in depressed patients and healthy controls. In contrast, acute antidepressant treatment induces an activation of basal HPA axis activity. OBJECTIVES: We examined the effects of 4 days of treatment with the selective serotonin reuptake inhibitor, citalopram, on basal salivary cortisol and on suppression of salivary cortisol by prednisolone. METHODS: We used a single-blind, placebo-controlled, repeated-measure design. Salivary cortisol was measured from 0900 to 1700 hours. In the first phase of the study, basal salivary cortisol secretion was measured on 2 study days, before and after 4 days of treatment with citalopram (orally, 20 mg/day). In the second phase, salivary cortisol secretion after suppression by prednisolone (5 mg, given at 2200 hours the night before) was measured on 2 study days, again before and after 4 days of treatment with citalopram (orally, 20 mg/day). Eight volunteers participated to the study. RESULTS: Citalopram increased basal salivary cortisol in the morning (0900-1100 hours) by approximately 47% (P=0.003). Moreover, citalopram increased suppression by prednisolone in the morning (0900-1100 hours): suppression was approximately 22% before citalopram and 45% after citalopram (P=0.05). CONCLUSIONS: Citalopram increases glucocorticoid-mediated negative feedback on the HPA axis after as little as 4 days of treatment. This effect could be due to an increased function of the corticosteroid receptors. Our findings further support the notion that one of the mechanisms by which antidepressants exert their therapeutic effects is by normalizing HPA axis hyperactivity in depressed patients.

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citalopram escitalopram Lexapro
The selective serotonin reuptake inhibitor citalopram increases fear after acute treatment but reduces fear with chronic treatment: a comparison with tianeptine.

Burghardt NS, Sullivan GM, McEwen BS, Gorman JM, LeDoux JE.

W.M. Keck Foundation Laboratory of Neurobiology, Center for Neural Science, New York University, New York, New York 10003, USA.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are efficacious in the treatment of a variety of fear or anxiety disorders. Although they inhibit the reuptake of serotonin within hours of administration, therapeutic improvement only occurs after several weeks. In this study, we used fear conditioning to begin to understand how acute and chronic SSRI treatment might differentially affect well-characterized fear circuits. METHODS: We evaluated the effects of acute and chronic treatment with the SSRI citalopram on the acquisition of auditory fear conditioning. To further understand the role of serotonin in modulating fear circuits, we compared these effects with those of acute and chronic administration of the antidepressant tianeptine, a purported serotonin reuptake enhancer. RESULTS: We found that acute administration of the SSRI citalopram enhanced acquisition, whereas chronic treatment reduced the acquisition of auditory fear conditioning. In comparison, treatment with tianeptine had no effect acutely but also reduced the acquisition of tone conditioning when administered chronically. CONCLUSIONS: Our findings with citalopram are consistent with the clinical effects of SSRI treatment seen in patients with anxiety disorders, in which anxiety is often increased during early stages of treatment and decreased after several weeks of treatment. The findings also indicate that auditory fear conditioning can be a useful tool in understanding differences in the effects of short-term and long-term antidepressant treatment with serotonergic medications. Copyright 2004 Society of Biological Psychiatry

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citalopram escitalopram Lexapro
Hippocampal brain-derived neurotrophic factor expression following treatment with reboxetine, citalopram, and physical exercise.

Russo-Neustadt AA, Alejandre H, Garcia C, Ivy AS, Chen MJ.

Department of Biological Sciences, California State University, Los Angeles, CA 90032, USA. arusson calstatela.edu

The antidepressants, reboxetine and citalopram, were used in conjunction with voluntary physical exercise (wheel running) in order to assess the contribution of noradrenergic and serotonergic activation to enhancements in hippocampal brain-derived neurotrophic factor (BDNF) expression resulting from antidepressant treatment and exercise. Reboxetine (40 mg/kg/day), citalopram (10 mg/kg/day), voluntary physical activity, and the combination of antidepressants with exercise were applied to rats for a range of treatment intervals (2 to 14 days). Hippocampal BDNF transcription levels (full-length BDNF, as well as exons I-IV) were then assessed via in situ hybridization.Reboxetine treatment led to a rapid (evident at 2 days) enhancement in BDNF transcription in several hippocampal regions. This increase was also observed when reboxetine treatment was combined with voluntary physical activity for 2 weeks. Treatment with citalopram led to an increase in BDNF mRNA in only one hippocampal region (CA2) after short-term (2 days) treatment, and when combined with exercise, increased BDNF mRNA in the CA4 and dentate gyrus after 2 weeks. As reported in previous studies, voluntary physical activity enhanced BDNF transcription in several hippocampal areas, both on its own and in combination with antidepressant treatments. Examination of the levels of individual BDNF transcript variants influenced by each of these antidepressants revealed distinct patterns of expression in response to the various treatments, and showed that exercise-plus-antidepressant produced significant changes where antidepressant alone failed. Overall, treatment with the norephinephrine-selective antidepressant, reboxetine, in combination with exercise, led to both rapid and sustained increases in hippocampal BDNF mRNA expression. The serotonergic agent, citalopram, appeared to require longer treatment intervals in order to influence BDNF expression positively.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15199375&dopt=Abstract citalopram escitalopram Lexapro