Forced Swimming Test In Rats Research Articles

The involvement of serotonergic system in the antidepressant effect of zinc in the forced swim test

Recent preclinical data indicated the antidepressant-like activity of zinc in different tests and models of depression. The present study investigates the involvement of the serotonergic system in zinc activity in the forced swim test (FST) in mice and rats. The combined treatment of sub-effective doses of zinc (hydroaspartate, 2.5 mg Zn/kg) and citalopram (15 mg/kg), fluoxetine (5 mg/kg) but not with reboxetine (2.5 mg/kg) significantly reduces the immobility time in the FST in mice. These treatments had no influence on the spontaneous locomotor activity. Moreover, while the antidepressant-like effect of zinc (5 mg/kg) in the FST was significantly blocked by pretreatment with inhibitor of serotonin synthesis, p-chlorophenylalanine (pCPA, 3 × 200 mg/kg), 5HT-2 A/C receptor antagonist, ritanserin (4 mg/kg) or 5HT-1A receptor antagonist, WAY 1006335 (0.1 mg/kg), the zinc-induced reduction in the locomotor activity was not affected by these serotonin modulator agents. These results indicate the specific involvement of the serotonergic system in antidepressant but not the motion behavior of zinc in mice. Also, an increase in the swimming but not climbing parameter of the rat FST observed following zinc administration (2.5 and 5 mg Zn/kg) indicates the serotonin pathway participation. This present data indicates that the antidepressant-like activity of zinc observed in the FST involves interaction with the serotonergic system.

Effects of Acute and Chronic Stressors and CRF in Rat and Mouse Tests for Depression

Depressive illness is frequently associated with life stress. Corticotropin-releasing factor (CRF) is believed to be a key brain mediator of behaviors associated with stress, and abnormalities in the function of CRF have been associated with depression. Therefore, we have studied the effects of acute and chronic footshock and restraint in tests used in rodents to assess depression-like activity and antidepressant effects: the forced swim test in rats and mice, and the tail suspension test in mice. We also tested the effect of intracerebroventricular (icv) CRF administration. The results were complex. In the forced swim test in rats, acute footshock and restraint reduced floating, whereas chronic footshock increased floating as did icv CRF. However, chronic restraint induced opposite effects, decreasing floating in the forced swim test. The results from mice were significantly different. In the forced swim test, acute footshock and restraint decreased floating, while chronic footshock increased floating, and chronic restraint decreased floating as it did in rats. However, icv CRF decreased floating. The results from the tail-suspension test paralleled those from the forced swim test except that chronic footshock tended to decrease the time spent immobile. Thus in rats, the behavioral effects of the chronic footshock in the forced swim test could be explained by a desensitization of the CRF systems, either decreased activation of CRF, or desensitization of its receptors. However, such an effect cannot explain the responses to restraint, nor the behavioral effects of chronic footshock and restraint in mice.

TC-5214 (S-(+)-mecamylamine): a neuronal nicotinic receptor modulator with antidepressant activity.

Both clinical and preclinical data support a potential therapeutic benefit of modulating the activity of CNS neuronal nicotinic receptors (NNRs) to treat depression and anxiety disorders. Based on the notion that the depressive states involve hypercholinergic tone, we have examined the potential palliative role of NNR antagonism in these disorders, using TC-5214 (S-(+) enantiomer of mecamylamine), a noncompetitive NNR antagonist. TC-5214 demonstrated positive effects in a number of animal models of depression and anxiety. TC-5214 was active in the forced swim test in rats (minimum effective dose (MED)=3 mg/kg i.p.), a classical depression model. It was also active in the behavioral despair test in mice (0.1-3.0 mg/kg i.p.), another model of depression. In the social interaction paradigm in rats, a model of generalized anxiety disorder (GAD), TC-5214 was active at a dose of 0.05 mg/kg s.c. In the light/dark chamber paradigm in rats, a model of GAD and phobia, TC-5214 was also active at a dose of 0.05 mg/kg s.c. Although TC-5214 shows modest selectivity among NNR subtypes, the antidepressant and anxiolytic effects seen in these studies are likely attributable to antagonist effects at the alpha4beta2 NNRs. This is supported by the observation of similar effects with alpha4beta2-selective partial agonists such as cytisine and with alpha4beta2-selective antagonists such as TC-2216. TC-5214 was well tolerated in acute and chronic toxicity studies in mice, rats, and dogs, showed no mutagenicity and displayed safety pharmacology, pharmacokinetic and metabolic profiles appropriate for therapeutic development. Overall, the results support a novel nicotinic cholinergic antagonist mechanism for antidepressant and anxiolytic effects and highlight the potential of NNR antagonists such as TC-5214 as therapeutics for the treatment of anxiety and depression.

Antidepressant behavioral effects of duloxetine and amitriptyline in the rat forced swimming test

To compare the effects of the antidepressant drugs duloxetine and amitriptyline on depressive behaviors in rats. Fifteen male Wistar rats were given systemic injections of duloxetine, amitriptyline or saline prior to a Forced Swimming Test (FST). Immobility and number of stops were measured. Data were analyzed by one-way ANOVA and Kruskall-Wallis. Rats given injections of duloxetine displayed fewer stops than the amitriptyline and control group (p< 0.05). The control group and Amitriptyline showed no difference (p=0.8). Duloxetine reduced depressive behaviors in the Forced Swimming Test been more effective than amitriptyline.

Stressors can affect immobility time and response to imipramine in the rat forced swim test

We subjected Wistar rats to the forced swim test (FST) to compare the effects of two doses of imipramine in physically stressed rats (P: unavoidable electric footshocks), emotionally stressed rats (E: odors), or non-stressed rats (C). Stress or control sessions lasted 35 days. Drug treatments began on day 21 and continued for the next 14 days. E rats were placed for 10 min, once per day for 35 days, in a small non-movement-restricting cage impregnated with urine collected from a P rat. E and P rats exhibited opposite changes in locomotion. After 21 days of stress sessions, P rats displayed the longest immobility times in the FST, followed by E rats. In the P group, on day 7 of treatment (day 28 of the study), imipramine (2.5 mg/kg) reduced immobility time to baseline values. In the E group, immobility time decreased only after 14 days of treatment with the low imipramine dose. The high dose of imipramine (5.0 mg/kg) reduced immobility time at day 7 of treatment in all groups. In conclusion, physical and emotional stress similarly increased immobility time in the FST, but emotional stress appears to be more resistant to imipramine treatment.

Frequency of climbing behavior as a predictor of altered motor activity in rat forced swimming test

Previous work has shown that the frequency of climbing behavior in rats submitted to the forced swimming test (FST) correlated to the section's crosses in the open field test, which suggest it might be taken as a predictor of motor activity in rat FST. To investigate this proposal, the frequency, duration, as well as the ratio duration/frequency for each behavior expressed in the FST (immobility, swimming and climbing) were compared in animals treated with a motor stimulant, caffeine (CAF), and the antidepressant, clomipramine (CLM). Male Wistar rats were submitted to 15 min of forced swimming (pre-test) and 24 h later received saline (SAL, 1 ml/kg, i.p.) or CAF (6.5 mg/kg, i.p.) 30 min prior a 5-min session (test) of FST. To validate experimental procedures, an additional group of rats received three injections of SAL (1 ml/kg, i.p.) or clomipramine (CLM, 10 mg/kg, i.p.) between the pre-test and test sessions. The results of the present study showed that both drugs, CLM and CAF, significantly reduced the duration of immobility and significantly increased the duration of swimming. In addition, CAF significantly decreased the ratio of immobility, and CLM significantly increased the ratio of swimming and climbing. Moreover, CLM significantly increased the duration of climbing but only CAF increased the frequency of climbing. Thus, it seems that the frequency of climbing could be a predictor of altered motor activity scored directly in the FST. Further, we believe that this parameter could be useful for fast and reliable discrimination between antidepressant drugs and stimulants of motor activity.

Antidepressant-like effects of sodium butyrate in combination with estrogen in rat forced swimming test: Involvement of 5-HT 1A receptors

Sodium butyrate (NaB), a histone deacetylase inhibitor, has been implicated in the antidepressant-like effects either injected as a single drug or in combination with selective serotonin reuptake inhibitor (SSRI), such as fluoxetine. Estrogen is also demonstrated to have antidepressant effect especially together with fluoxetine. We investigated whether NaB administered in combination with estradiol benzoate (EB) exerted antidepressant-like effect in forced swimming test (FST) in ovariectomized female rats. Furthermore, we detected the mRNA expressions of serotonin receptors and neuropeptides in hypothalamus, both of which participate in the mood disorder. Ovariectomized female SD rats were treated with vehicle, NaB, EB or NaB combined with EB for 7 days and then subjected to FST. The expressions of serotonin receptors (5-hydroxytryptamine receptor), corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) mRNA in the hypothalamus were detected by real time PCR. We found that co-treated with NaB and EB resulted in a significant decrease in immobility behavior in FST, a measure for depression-like behavioral. 5-HT 1A antagonist, WAY 100635, significantly block the antidepressant-like effects induced by NaB plus EB. The mRNA expression of the serotonin-1A [5-hydroxytryptamine 1A (5-HT 1A)] receptor was increased in the co-treated group in hypothalamus, while there was no difference in the mRNA expression of 5-HT 2A or 5-HT 2C. The mRNA expression of CRH or AVP was not significantly altered either. In conclusion, NaB may exert antidepressant-like effects in combination with EB in ovariectomized female rats through 5-HT 1A receptor, via altering the expression of 5-HT 1A in the hypothalamus.

Involvement of l-arginine–nitric oxide–cyclic guanosine monophosphate pathway in the antidepressant-like effect of tramadol in the rat forced swimming test

Tramadol is a centrally acting analgesic which is used mainly for the treatment of moderate or severe pain. It is a synthetic opioid in the aminocyclohexanol group that binds weakly to μ-opioid receptors. Since it has been suggested that both opioid and monoaminergic systems play a role in depressive disorders, tramadol has been studied in the forced swimming test (FST). The present study was designed to explore the antidepressant activity of tramadol in rat FST and its possible mechanisms of action. The involvement of l-arginine–nitric oxide (NO)–cyclic guanosine monophosphate (cGMP) signaling pathway in the antidepressant action of tramadol was investigated. Treatment with tramadol, given (30 min earlier) by oral route (p.o.) at the doses of 10, 20 and 40 mg/kg, decreased immobility time in the FST. Pretreatment of rats with l-arginine (250 mg/kg, intraperitoneal, i.p., a nitric oxide precursor) or sildenafil (5 mg/kg, i.p., a phosphodiesterase 5 inhibitor, PDE5) significantly reversed the reduction in immobility time elicited by tramadol (20 mg/kg, p.o.) in the FST. Treatment of animals with a sub-effective dose of tramadol (5 mg/kg, p.o.) produced a synergistic antidepressant-like effect with N G-nitro- l-arginine (L-NNA, 3 mg/kg, i.p., an inhibitor of nitric oxide synthase) or with 7-nitroindazole (7-NI, 9 mg/kg i.p., a specific neuronal nitric oxide synthase inhibitor) in the FST. Pretreatment of animals with methylene blue (3.75 mg/kg i.p., an inhibitor of NO synthase and soluble guanylate cyclase — sGC) or (1 H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one) (ODQ, 2 mg/kg, i.p., a specific inhibitor of sGC) significantly caused a synergistic effect with a sub-effective dose of tramadol (5 mg/kg, p.o.) in the FST. In the present study, different doses of tramadol and the combination with the l-arginine–NO–cGMP pathway modulators had no effect on the locomotor activity of rats in the open-field test. Thus, our findings suggest that the acute administration of tramadol produces antidepressant-like effect in the rat FST by a mechanism that involves the inhibition of l-arginine–NO–cGMP pathway.

Antidepressant-Like Pharmacological Profile of a Novel Triple Reuptake Inhibitor, (1S,2S)-3-(Methylamino)-2-(naphthalen-2-yl)-1-phenylpropan-1-ol (PRC200-SS)

Due to the putative involvement of dopaminergic circuits in depression, triple reuptake inhibitors are being developed as a new class of antidepressant, which is hypothesized to produce a more rapid onset and better efficacy than current antidepressants selective for serotonin or norepinephrine neurotransmission. (1S,2S)-3-(Methylamino)-2-(naphthalen-2-yl)-1-phenylpropan-1-ol (PRC200-SS), a new triple reuptake inhibitor, potently bound to the human serotonin, norepinephrine, and dopamine transporters with K(d) values of 2.3, 0.63, and 18 nM, respectively. Inhibition of serotonin, norepinephrine, and dopamine uptake by PRC200-SS was also shown in cells expressing the corresponding transporter (K(i) values of 2.1, 1.5, and 61 nM, respectively). In vivo, PRC200-SS dose-dependently decreased immobility in the forced-swim test in rats and in the tail-suspension test in mice, models predictive of antidepressant activity, with effects comparable with imipramine. These results in the behavioral models did not seem to result from the stimulation of locomotor activity. Consistent with the in vitro data and behavioral effects, peripheral administration of PRC200-SS (5 and 10 mg/kg i.p.) significantly increased extracellular levels of serotonin and norepinephrine in the medial prefrontal cortex, and of serotonin and dopamine in the core of nucleus accumbens, with reduction of levels of 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindoleacetic acid compared with levels for saline control. Furthermore, PRC200-SS self-administration, which was used as a marker of abuse liability, was not observed with rats. Therefore, it seems that PRC200-SS may represent a novel triple reuptake inhibitor and possess antidepressant activity.

P.2.d.017 Ketanzerine modulates expression of 5-HT2A/2C- and 17b-estradiol receptors mRNAs in female rats in forced swim test

P.2.d.017 Ketanzerine modulates expression of 5-HT2A/2C- and 17b-estradiol receptors mRNAs in female rats in forced swim test

Antidepressant-like behavioral effects of IGF-I produced by enhanced serotonin transmission

Previous research has suggested that mobilization of neurotrophic factors, such as insulin-like growth factor I (IGF-I), can be involved in the effects of antidepressant treatments. The current experiments showed that IGF-I leads to antidepressant-like effects in the modified rat forced swim test when tested 3 days, but not 1 day, after i.c.v. administration. These effects were sustained longer than the antidepressants paroxetine and desipramine. In addition, blockade of the IGF-I receptor with the IGF-I antagonist JB1 30 min before IGF-I administration prevented the antidepressant-like effects of IGF-I. However, when JB1 was administered 3 days after IGF-I administration and 30 min prior to testing, the antidepressant-like effects of IGF-I were still present suggesting that IGF-1 produces a long-term activation of neural systems involved in the antidepressant response. Because the pattern of antidepressant-like effects of IGF-I resembled those of selective serotonin reuptake inhibitors, the role of serotonin in the behavioral effects of IGF-I was studied. Depletion of serotonin, by the tryptophan hydroxylase inhibitor para-chlorophenylalanine, blocked the antidepressant-like effects of IGF-I. Administration of IGF-I increased basal serotonin levels in the ventral hippocampus and altered the effects of acute citalopram. IGF-I administration did not change hippocampal cell proliferation at the 3-day timepoint when behavioral effects were seen. In addition, IGF-I did not alter the expression of mRNA levels of tryptophan hydroxylase or SERT in the brain stem, or [ 3H] citalopram binding in the hippocampus or cortex. Thus, IGF-I administration initiates a long-lasting cascade of neurochemical effects involving increased serotonin levels that results in antidepressant-like behavioral effects.

Antidepressant activity of acoustical neuro-modulation in comparison with well-known antidepressants in forced swim test in rats

Antidepressant activity of acoustical neuro-modulation in comparison with well-known antidepressants in forced swim test in rats

Influence of gender and estrous cycle in the forced swim test in rats.

The present work aimed at studying the influence of the estrous cycle in the forced swim test, an animal model of depression. For this, 44 male and female Wistar rats were divided into five groups according to the hormonal state in the first day of the study: metaestrus (N = 12), diestrus (N = 8), proestrus (N = 7), estrous (N = 6) and males (N = 11). They were housed in groups of five, with water and food ad libitum under a 12/12 h light/dark cycle. Females were screened daily for the estrous cycle. The animals were subjected to two swimming sessions in a glass cylinder with water up to 15 cm at 28±2o C. The data of the first five minutes of a 15-min first session were compared to those of a 5-min second session 24 h later. The results indicate that the latency to the first immobility was substantially reduced in the second session and was longer for females in diestrus and proestrus in the first session. The results also indicate that females in diestrus and proestrus exhibited less immobility than males in the first session; females in diestrus also exhibited less immobility than females in metaestrus. Females in metaestrus and diestrus, as well as males, did not present the decrease in total immobility times in the second session. The present results are analyzed in terms of differential effects of progesterone and estrogen on a learning component and an affective component.

S32006, a novel 5-HT2C receptor antagonist displaying broad-based antidepressant and anxiolytic properties in rodent models

Serotonin (5-HT)(2C) receptors are implicated in the control of mood, and their blockade is of potential interest for the management of anxiodepressive states. Herein, we characterized the in vitro and in vivo pharmacological profile of the novel benzourea derivative, S32006. Standard cellular, electrophysiological, neurochemical, and behavioral procedures were used. S32006 displayed high affinity for human (h)5-HT(2C) and h5-HT(2B) receptors (pK (i)s, 8.4 and 8.0, respectively). By contrast, it had negligible (100-fold lower) affinity for h5-HT(2A) receptors and all other sites examined. In measures of Gq-protein coupling/phospholipase C activation, S32006 displayed potent antagonist properties at h5-HT(2C) receptors (pK (B) values, 8.8/8.2) and h5-HT(2B) receptors (7.8/7.7). In vivo, S32006 dose-dependently (2.5-40.0 mg/kg, i.p. and p.o.) abolished the induction of penile erections and a discriminative stimulus by the 5-HT(2C) receptor agonist, Ro60,0175, in rats. It elevated dialysis levels of noradrenaline and dopamine in the frontal cortex of freely moving rats, and accelerated the firing rate of ventrotegmental dopaminergic and locus ceruleus adrenergic neurons. At similar doses, S32006 decreased immobility in a forced-swim test in rats, reduced the motor depression elicited by 5-HT(2C) and alpha(2)-adrenoceptor agonists, and inhibited both aggressive and marble-burying behavior in mice. Supporting antidepressant properties, chronic (2-5 weeks) administration of S32006 suppressed "anhedonia" in a chronic mild stress procedure and increased both expression of BDNF and cell proliferation in rat dentate gyrus. Finally, S32006 (0.63-40 mg/kg, i.p. and p.o) displayed anxiolytic properties in Vogel conflict and social interaction tests in rats. S32006 is a potent 5-HT(2C) receptor antagonist, and possesses antidepressant and anxiolytic properties in diverse rodent models.

D-161, a novel pyran-based triple monoamine transporter blocker: Behavioral pharmacological evidence for antidepressant-like action

Deficiency in dopaminergic activity has been linked to a depressed state in pharmacological and clinical studies. Current pharmacological treatment for depression primarily involves modulation of serotonergic and noradrenergic systems but not dopaminergic neurotransmission. Available pharmacotherapy for depression has a number of drawbacks as a significant number of people are either refractory or develop tolerance to the antidepressant agents resulting in relapse. Furthermore, the slow onset of action of current therapies often poses a challenge for effective treatment. In our effort to develop novel molecules impacting all three above mentioned monoamine systems, we discovered structurally unique pyran derivatives with various profiles in inhibiting monoamine transporters. One of our lead molecules, D-161 exhibited triple monoamine transporter inhibitory activity with the highest affinity for norepinephrine transporter (NET) followed by its affinity for serotonin transporter (SERT) and dopamine transporter (DAT). D-161 exhibited potent activity in reducing immobility significantly in the rat forced swim test as well as in the mouse tail suspension test. Moreover, results from locomotor activity tests indicated that the reduction of immobility by D-161 was not due to motor activation as no significant motor activation was observed when the rats were subjected to the same doses of drug under the same conditions as in the forced swim test. These results suggest that the novel asymmetric pyran derivative D-161 with unique molecular structure exhibiting triple monoamine transporter inhibitory activity could possess potent antidepressant activity.

Neuronal NOS inhibitor 1-(2-trifluoromethylphenyl)-imidazole augment the effects of antidepressants acting via serotonergic system in the forced swimming test in rats

Treatment-resistant depression has necessitated new therapeutic strategies in augmenting the therapeutic actions of currently existing antidepressant drugs. The aim of this study was to investigate the possibility of synergistic interaction between 1-(2-trifluoromethylphenyl)-imidazole (TRIM), a novel neuronal nitric oxide synthase (nNOS) inhibitor and conventional antidepressants of different classes in the forced swimming test (FST) in rats. TRIM decreased the immobility time at 50 mg/kg doses in the FST in rats. Treatment with a behaviourally subeffective dose of TRIM (20 mg/kg) augmented the behavioural effect of tricyclic antidepressant imipramine, selective serotonin re-uptake inhibitor (SSRI) citalopram and fluoxetine or selective serotonin reuptake enhancer tianeptine but failed to augment the antidepressant effect of reboxetine, a noradrenaline re-uptake inhibitor, in this test. Therefore inhibition of NOS augments the effects of antidepressants acting on serotonergic system in the FST. Neither TRIM (10–50 mg/kg) nor other drug treatments affected the locomotor activity of animals. These findings are in agreement with the view that antidepressant effects or augmentation of these effects in the FST may be explained with inhibition of NOS activity and this may be a new approach in offering greater therapeutic efficacy of antidepressants acting via serotonergic system.

Dopamine D2/D3 receptor agonists produce antidepressant‐like effects in the rat forced swim test through co‐activation of both receptor subtypes

Dopamine D2/D3 receptor agonists have been shown to have antidepressant actions in clinical and preclinical studies; however, the dopamine receptor subtype that mediates the antidepressant effects is unknown. The present study investigated the antidepressant‐like effects of dopamine D1‐, D2‐, D3‐, and D4‐preferring agonists in the rat forced swim test and the role of different dopamine receptor subtypes in these behavioral effects. The dopamine D3‐preferring agonists (PD‐128,907, pramipexole, quinpirole, and apomorphine), the D2‐preferring agonist (sumanirole), and the dopamine D1 agonist (SKF81297), but not the D4 agonist (ABT‐724), decreased immobility in the forced swim test, indicating an antidepressant profile of action. The D2 antagonist L‐741,626 and the D3 antagonist PGO1037, but not the D1 antagonist SCH23390, attenuated the antidepressant effects of the D2/D3 agonists. These data suggest that antidepressant actions of dopamine D2/D3 agonists require the activation of both D2 and D3 receptor subtypes and blockade of either receptor subtype eliminates the antidepressant effects. This work was supported by USPHS grants DA00254, DA020669, T32 GM07767, T32 DA07267, and T32 DA07268.

Antidepressant-like activity of 8-Br-cAMP, a PKA activator, in the forced swim test

The PKA activator, 8-Br-cAMP, dose-dependently reduced the immobility time in the forced swim test in rats. This effect was antagonized by co-treatment with selective PKA inhibitor Rp-cAMPS. This is the first demonstration of the antidepressant-like activity of the PKA activator.

Contribution of the dopaminergic system to the effect of chronic fluoxetine in the rat forced swim test.

administration of selective serotonin reuptake inhibitors (SSRI) enhances dopaminergic activity. However, the role of enhanced dopaminergic transmission in the therapeutic effects of this kind of antidepressants is still unclear. Drugs producing dopaminergic activation lead to an increment in general activity. Thus, it is reasonable to assume that some of the therapeutic effects of SSRIs are due to dopaminergic enhanced functionality. The forced swim test (FST) is a widely used test in the screening of new compounds with potential antidepressant activity. In this study the effects of pretreatment with low doses of the DA release inductor cocaine and the D2, D3 and D4 antagonist haloperidol were analyzed in the FST on rats submitted to chronic intragastric administration of the SSRI fluoxetine. Our results show that animals treated with fluoxetine and pre-treated with cocaine had significantly higher latencies than saline or haloperidol pre-treated subjects. Among both fluoxetine and saline treated animals, those pre-treated with cocaine had significant lesser immobility time. Haloperidol pre-treated animals had significantly higher immobility time than those pre-treated with saline. From these results, it is clear that the pharmacological modification of dopaminergic systems leads to behavioral changes in rats treated with both saline and fluoxetine. The FST does not have enough precision as to distinguish between dopaminergic and non- dopaminergic components in the antidepressant effects of SSRIs, for this reason the use of the FST in combination to other models is mandatory. Keywords: forced swim test, antidepressant, fluoxetine, cocaine, haloperidol.

The selective 5-HT 6 receptor antagonist SB-399885 enhances anti-immobility action of antidepressants in rats

The aim of the present study was to investigate the effect of antidepressant drugs (characterized by a different mechanism of action), administered jointly with the selective 5-HT 6 receptor antagonist N-[3,5-dichloro-2-(methoxy)phenyl]-4-(methoxy)-3-(1-piperazinyl)benzenesulfonamide (SB-399885), in the forced swim test in rats. All the compounds under study were given intraperitoneally in doses which did not shorten the immobility time of rats. Co-administration of SB-399885 (3 mg/kg) and imipramine (20 mg/kg), desipramine (20 mg/kg), bupropion (5 mg/kg) or moclobemide (20 mg/kg), produced significant anti-immobility action, whereas SB-399885 (3 mg/kg) given jointly with citalopram (20 mg/kg) did not affect immobility time. None of the compounds studied, given alone or jointly, increased the general activity of rats measured in the open field test. The obtained results indicate that the blockade of 5-HT 6 receptors may facilitate the anti-immobility effect of imipramine, desipramine, bupropion or moclobemide in the forced swim test.