citalopram Celexa
Nicotine and nicotinic receptor antagonists potentiate the antidepressant-like effects of imipramine and citalopram.

Popik P, Kozela E, Krawczyk M.

Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna street, 31-343 Krakow, Poland. nfpopik cyf-kr.edu.pl

1. Epidemiological and clinical observations suggest the involvement of nicotinic acetylcholine receptors (nAChRs) in depressive illness. Nonetheless, there is no clearcut evidence that nicotine and/or nAChR antagonists produce an antidepressant effect. 2. In the tail-suspension test (C57/Bl male mice), nicotine (0.8-1.2 mg kg(-1) s.c. or i.p.) given 15-60 min before the measurement exerted no effect on immobility. 3. Given 30 min before the measurement, citalopram (2 mg kg(-1)) produced a slight decrease in immobility; coadministration of nicotine (0.8 mg kg(-1), 15 but not 40 min before the test) to citalopram-treated mice resulted in a robust decrease in immobility. Imipramine (4 mg kg(-1)) did not affect immobility, but given in combination with 0.8 mg kg(-1) of nicotine (15 but not 40 min before the test), a decrease in immobility was observed. Nicotine (0.8 and 1.2 mg kg(-1)) also produced an enhancement in the anti-immobility effect of imipramine (20 mg kg(-1)). 4. We further investigated if nAChR antagonists would influence the antidepressant-like effects of imipramine and citalopram. Unexpectedly, mecamylamine (1-2.5 mg kg(-1)) and dihydro-beta-erythroidine (2 mg kg(-1)) potentiated the antidepressant-like effect of imipramine (4-20 mg kg(-1)). Mecamylamine (2.5 mg kg(-1)) but not dihydro-beta-erythroidine also increased the antidepressant-like effect produced by 2 mg kg(-1) of citalopram. 5. The interaction between nAChR antagonists and antidepressants appeared synergistic. 6. Neither nAChR ligands, antidepressants nor combinations of the two, affected locomotor activity. 7. The present results demonstrate an unexpected interaction between nAChR ligands and imipramine and citalopram in the tail-suspension test.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12871839&dopt=Abstract citalopram Celexa



citalopram Celexa
Repeated citalopram treatment but not stress exposure attenuates hypothalamic-pituitary-adrenocortical axis response to acute citalopram injection.

Moncek F, Duncko R, Jezova D.

Institute of Experimental Endocrinology, Slovak Academy of Sciences, Vlarska 3, 83306 Bratislava, Slovakia.

Many experimental, clinical and epidemiological studies have shown a direct connection between exposure to stress or adverse life events and disease, but little is known about the effect of stress on the action of drugs. The aim of this study was to test the hypothesis that previous exposure to stress changes the action of the antidepressant drug citalopram (10 mg/kg, i.p.) on hypothalamic-pituitary-adrenocortical (HPA) axis function, gene expression of selected neuropeptides and serotonin reuptake. Three different stress models were used, which included immobilization, restraint and unpredictable stress stimuli. Samples of plasma for hormone measurement were taken from conscious cannulated animals. Changes in corticotropin-releasing hormone (CRH) and proopiomelanocortin (POMC) gene expression in the paraventricular nucleus of the hypothalamus and the anterior pituitary, respectively, and the ability of citalopram to inhibit serotonin reuptake were investigated. The exposure to three different stress models did not influence citalopram action on individual parameters of HPA axis and on serotonin reuptake. On the other hand, repeated administration of the drug led to significant attenuation of ACTH and CRH mRNA responses. The present results allow to suggest that the stressors used did not influence serotonergic neurotransmission to the extent that would modify HPA axis response to citalopram challenge. Activation of HPA axis by acute citalopram treatment was found to be accompanied by increased CRH gene expression in the hypothalamus. Repeated administration of the drug led to the development of tolerance to activation of central and peripheral components of HPA axis, but not to serotonin reuptake inhibition.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12527033&dopt=Abstract citalopram Celexa



citalopram Celexa
Increased extracellular serotonin level in rat hippocampus induced by chronic citalopram is augmented by subchronic lithium: neurochemical and behavioural studies in the rat.

Wegener G, Bandpey Z, Heiberg IL, Mork A, Rosenberg R.

Institute for Basic Psychiatric Research, Department of Biological Psychiatry, 8240, Risskov, Denmark. wegener dadlnet.dk

RATIONALE: A substantial number of patients do not respond sufficiently to antidepressant drugs and are therefore often co-medicated with lithium as an augmentation strategy. However, the neurochemical rationale behind this strategy needs to be further clarified. OBJECTIVES: We examined the effect of chronic citalopram and subchronic lithium, alone or in combination, on (a) serum levels of citalopram and lithium, (b) animal behaviour and (c) hippocampal serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels. Furthermore, we examined the serum level of citalopram and hippocampal 5-HT following one acute citalopram injection. METHODS: Microdialysis in the freely moving animals was used to determine hippocampal 5-HT and 5-HIAA. The animal behaviour was examined in the open field and forced swim test. RESULTS. We found that chronic administration of citalopram (20 mg/kg/24 h s.c.) significantly increased the 5-HT baseline relative to vehicle-treated rats. Addition of subchronic lithium (60 mmol/kg chow pellet p.o.) to chronic citalopram therapy further elevated the 5-HT levels. Moreover, we found acute citalopram (5 mg/kg s.c.) to increase the 5-HT level. The immobility time in the FST and the locomotion in the OF were unaffected by any treatments. CONCLUSIONS: The present results support the assumption that increases in hippocampal 5-HT neurotransmission may be important in the augmentatory effect of lithium.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12552361&dopt=Abstract citalopram Celexa



citalopram Celexa
Carbonic anhydrase activators. The selective serotonin reuptake inhibitors fluoxetine, sertraline and citalopram are strong activators of isozymes I and II.

Casini A, Caccia S, Scozzafava A, Supuran CT.

Universita degli Studi di Firenze, Dipartimento di Chimica, Rm 188, Via della Lastruccia 3, I-50019 (Firenze), Sesto Fiorentino, Italy.

The selective serotonin reuptake inhibitors (SSRI) fluoxetine, sertraline and citalopram have been investigated for their ability to activate two carbonic anhydrase (CA) isozymes, hCA I and hCA II, in parallel with two standard activators for which the X-ray structure (in complex with isozyme II) has been resolved: histamine and phenylalanine. All three SSRI activated both isozymes with potencies comparable to that of the standards although the profile was different: for hCA I, best activators were fluoxetine and histamine, with citalopram and sertraline showing weaker activity. For hCA II, the best activators were phenylalanine and citalopram, and the weakest histamine and sertraline, whereas fluoxetine showed an intermediate behavior. These results suggest that SSRI efficacy in major depression complicating Alzheimer's disease may be partly due to their ability to activate CA isozymes and may lead to the development of potent activators for the therapy of diseases associated with significant decreases in brain CA activity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12873510&dopt=Abstract citalopram Celexa



citalopram Celexa
Induction of Fos-like-immunoreactivity in the central extended amygdala by antidepressant drugs.

Morelli M, Pinna A, Ruiu S, Del Zompo M.

Department of Toxicology, University of Cagliari, Italy. morellim tin.it

The induction of the early gene c-fos was evaluated through Fos immunohistochemistry in areas belonging to the extended amygdala after acute administration of two antidepressants, citalopram and imipramine. Both citalopram and imipramine at the dose of 5 and 20 mg/kg, respectively, induced Fos-like immunoreactivity (FLI) in the central amygdaloid nucleus, lateral division of the bed nucleus of the stria terminalis (BSTL), and interstitial nucleus of the posterior limb of the anterior commissure (IPAC). The shell of the nucleus accumbens, which forms a continuum with the central extended amygdala, showed a decrease of FLI after administration of either citalopram or imipramine. The mechanism of action and the brain areas affected by antidepressants are still a matter of debate. By showing that the central extended amygdala is a common site of action for two different antidepressant types, these results provide new insight into the mechanism of action of antidepressants.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10025677&dopt=Abstract citalopram Celexa



citalopram Celexa
Alterations in serum and brain trace element levels after antidepressant treatment: part I. Zinc.

Nowak G, Schlegel-Zawadzka M.

Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland.

We have studied the effect of chronic treatment with imipramine, citalopram and electroconvulsive shock (ECS) on serum and brain zinc levels in rats. Chronic treatment with citalopram (but not with imipramine or ECS) significantly (approx 20%) increased the serum zinc level. Chronic treatment with both drugs slightly (by approx 10%) increase the zinc level in the hippocampus and slightly decreased it in the cortex, cerebellum and basal forebrain. Calculation of the ratio hippocampus/brain region within each group demonstrated a significantly (approx 20%) higher value after treatment with either imipramine or citalopram. Moreover, chronic ECS induced a significant increase (by 30%) in the zinc level in the hippocampus and also a slight increase (by 11-15%) in the other brain regions. Thus, these different antidepressant therapies induced an elevation of the hippocampal zinc concentration, which indicates a significant role of zinc in the mechanism of antidepressant therapy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10065601&dopt=Abstract citalopram Celexa



citalopram Celexa
Behavioral sensitization to nicotine is associated with behavioral disinhibition; counteraction by citalopram.

Olausson P, Engel JA, Soderpalm B.

Department of Pharmacology, Institute of Physiology and Pharmacology, Goteborg University, Sweden. peter.olausson pharm.gu.se

This study investigated the effects of repeated nicotine treatment on locomotor activity and behavioral inhibition, and the influence of citalopram on the behavioral effects obtained. Male rats received daily subcutaneous injections of vehicle + vehicle (veh + veh), citalopram (5.0 mg/kg) + vehicle (cit + veh), vehicle + nicotine (1.0 mg/kg; veh + nic) or citalopram + nicotine (cit + nic). Acutely, nicotine stimulated locomotor activity, and repeated daily nicotine injections sensitized veh + nic rats to the nicotine-induced locomotor stimulation after 5, 10 and 15 treatment days, whereas in cit + nic rats, the enhancement of nicotine-induced locomotion was suppressed. However, when challenged with nicotine after citalopram withdrawal (-36 h), the cit + nic treated animals were also observed to be sensitized. In the elevated plus-maze, repeated nicotine treatment produced behavioral disinhibition, measured as an increase of time spent in and entries made into open arms (%), and chronic citalopram treatment attenuated the expression of behavioral disinhibition. Moreover, the degree of nicotine sensitization correlated to the behavioral disinhibition observed. In summary, these findings suggest that behavioral sensitization to nicotine is associated with behavioral disinhibition and that chronic citalopram treatment counteracts the expression of both phenomena. Since citalopram is a highly selective serotonin reuptake inhibitor, the effects of citalopram may be due to a facilitation of serotonin neurotransmission caused by the chronic citalopram treatment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10102762&dopt=Abstract citalopram Celexa



citalopram Celexa
Oxytocin as a possible mediator of SSRI-induced antidepressant effects.

Uvnas-Moberg K, Bjokstrand E, Hillegaart V, Ahlenius S.

Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.

The nonapeptide oxytocin is released into systemic circulation in situations of psychosocial interaction, and has been shown to be involved in mechanisms of social bonding and social recognition in laboratory studies. In view of disturbances in psychosocial relationships being a triggering factor for depression and anxiety, it is interesting to note that experimental studies have shown oxytocin to possess antidepressant- and anxiolytic-like actions. Thus. in the present study we examined effects of the SSRI citalopram (20 mg/kg i.p.) on plasma oxytocin, acutely and upon repeated administration, in adult male Sprague-Dawley rats. Plasma oxytocin, and some functionally related peptides (CCK, gastrin, somatostatin and insulin), were measured by standard radioimmunoassay techniques. Acute citalopram administration produced a statistically significant increase in plasma oxytocin and CCK levels. Administration of citalopram for 14 days did not attenuate the oxytocin-releasing effect to a challenge dose of the SSRI zimeldine (20 mg/kg s.c.), whereas CCK levels were not increased after the subchronic citalopram treatment. Thus, the SSRI citalopram produces increased plasma oxytocin levels acutely, and there appears to be no or little tolerance to this effect upon repeated administration. There were no, or variable, effects on plasma levels of gastrin, somatostatin or insulin. It is suggested that oxytocin release is an important aspect of the pharmacological actions of SSRIs, and this could be an important contributory factor for the clinical profile of this group of antidepressants with particular efficacy in disorders of psychosocial origin.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10102788&dopt=Abstract citalopram Celexa