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PubMed1996

[Pharmaco-epidemiologic study of the use of antidepressant drugs in the general population].

The objective of this study was to evaluate the mode of prescription and the users of antidepressant agents. It consisted of an initial phase (survey of the general population), aimed at selecting a representative sample of antidepressants users by a mail questionnaire, without asking prescribers in order to avoid the bias inherent to such an approach. Results showed a current incidence of use of 2.75 % for the 8 main antidepressants, i.e. more than one million adults in France. The distribution of antidepressants showed Prozac in first place, followed by Anafranil, and Laroxyl, then Stablon, Athymil, Survector and Ludiomil. In more than 50 % of cases, antidepressants have been taken for a year or more, continuously of intermittently. They were prescribed by a general practitioner in 60 % of cases and a psychiatrist in 30 %. A second survey phase (telephone) undertaken by psychiatrists and involving a sample of this population enabled determination of the pathophysiological profile of consumers at the time of prescription of antidepressant treatment, using a validated diagnostic tool, the MINI. Taking all drugs together, results showed that prescription was within Marketing Authorization approved indications in about 65 % of cases (existence of depression 61 %, dysthymia 3 %, OCD 1 %). This study shows that, in 23 % of cases, antidepressants are not used in patients with one of the psychiatric diseases identified by the MINI but nevertheless suffering from pathophysiological symptoms (subsyndronic syndrome). It can be concluded that, in some subjects, antidepressants are used in non-identified disorders. It must also be recognized that, with 3 % of users, the population of individuals treated by antidepressants is less than that of patients suffering, in the general population, from depression (5 to 10 % per year, according to studies).

Adult↗

PubMed1982

Effects of acute and subacute antidepressant treatment on kindled seizures in rats.

The effects of acute and subacute administration of the tricyclic antidepressants imipramine and amitriptyline, and the atypical antidepressants mianserin and iprindole, on seizures kindled from the amygdala and the cortex were examined. Whereas amitriptyline selectively antagonized seizures kindled from the amygdala after a single dose, neither amitriptyline nor imipramine was any more effective in antagonizing seizures kindled from the amygdala than from the cortex following subacute treatment. Both acute and subacute administration of iprindole failed to significantly alter seizures kindled from either site. Although only the highest acute dose of mianserin tested selectively attenuated amygdaloid seizures, a lower dose that was ineffective when given acutely, was selective when given subacutely. In contrast to an earlier report, the present findings suggest that kindling may not be a particularly useful model for the evaluation of potential antidepressant agents.

Amitriptyline↗

PubMed2006

[Treatment for irritable bowel syndrome--psychotropic drugs, antidepressants and so on].

Irritable bowel syndrome (IBS) is a functional disease with good prognosis, which is diagnosed by exclusion of possible causative organic diseases. However, since the patients tend to have strong psychotic symptoms including anxiety, tension, depression, irritation and insomnia, this syndrome has to be elucidated as a psychosomatic disease. Although the symptoms are usually limited to gastrointestinal symptoms such as abdominal pain and abnormal bowel movements, many patients also manifest some kinds of psychiatric abnormalities such as hypochondria, depression, hysteria, panic disorder and posttraumatic stress disorder. Especially, the prevalence of depression is high. Therefore, use of psychotropic drugs is efficient in treating IBS. Antidepressant agents including tricyclic agents such as amitriptyline, trimipramine, imipramine, clomipramine, amoxapine and nortriptyline; tetracyclic antidepressant; antidepressants such as SSRI and SNRI; sulpiride; benzodiazepine class anxiolytic agents; tandospirone; and Chinese herbal medicine are being used. IBS is a stress-related disease. Therefore, in spite of the importance of pharmacotherapy, patients should also be instructed to avoid the stress that aggravates the symptoms in all aspects of daily life.

Antidepressive Agents↗

PubMedDate not supplied

cAMP-dependent phosphorylation system after short and long-term administration of moclobemide.

Accumulating evidence suggested that signal transduction cascade including protein phosphorylation is implicated in the neurochemical action of antidepressant agents. Clinical data indicated that moclobemide, a short acting and reversible inhibitor of monoamino oxidase type. A, is an effective antidepressant medication. However, little is known about the intracellular effects of this compound. Thus, in the present study we assessed the binding of cAMP to cAMP-dependent protein kinase (PKA) in rat cerebral cortex following short and long-term administration of moclobemide. The results showed that 21 days of treatment with moclobemide significantly increased the specific [32P]-cAMP covalent binding into the soluble 52-54 kDa cAMP-receptor. This effect was not seen following 1, 5 and 12 days of treatment. These findings suggest that PKA could be implicated in the biochemical effects of moclobemide.

Animals↗

PubMed2002

EEG correlates of acute and chronic paroxetine treatment in depression.

Single dose administration of efficacious antidepressant agents elicit characteristic pharmaco-electroencephalographic (EEG) profiles in healthy volunteers but acute and chronic pharmaco-EEG profiling of antidepressant action in depressed patients has been relatively lacking. This study sought to examine the quantitative topographic EEGs of depressed patients in response to paroxetine treatment. Thirty male patients, meeting DSM-IV criteria for major depression, were examined before and after a single 20 mg dose. These, and an additional 40 patients, were also assessed following 6 weeks of treatment. Eyes-closed resting EEG, collected from 21 scalp sites, was spectrally analyzed to yield regional measures of absolute/relative power and mean frequency in delta, theta, alpha, beta and total spectrum frequency bands. Chronic treatment resulted in a significant reduction in scores on the Hamilton Rating Scale for Depression (HAM-D), with 80% of treatment completers exhibiting a >50% reduction in depression ratings at the end of the 6th week. Acute paroxetine did not alter EEG in patients but chronic treatment was associated with significant alterations as shown by diffuse decreases in alpha power and increases in slow (delta and theta) and anterior fast (beta) wave power, Mean theta and alpha (occipital) frequency were slowed while mean total frequency was accelerated at frontal sites and decreased at occipital sites. The chronic pharmaco-EEG response pattern reflects both sedating and activating actions in regional specific areas which are relevant to the pathophysiology and the pharmacotherapeutic treatment of depression.

Adult↗

PubMed2000

Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus.

Recent studies suggest that stress-induced atrophy and loss of hippocampal neurons may contribute to the pathophysiology of depression. The aim of this study was to investigate the effect of antidepressants on hippocampal neurogenesis in the adult rat, using the thymidine analog bromodeoxyuridine (BrdU) as a marker for dividing cells. Our studies demonstrate that chronic antidepressant treatment significantly increases the number of BrdU-labeled cells in the dentate gyrus and hilus of the hippocampus. Administration of several different classes of antidepressant, but not non-antidepressant, agents was found to increase BrdU-labeled cell number, indicating that this is a common and selective action of antidepressants. In addition, upregulation of the number of BrdU-labeled cells is observed after chronic, but not acute, treatment, consistent with the time course for the therapeutic action of antidepressants. Additional studies demonstrated that antidepressant treatment increases the proliferation of hippocampal cells and that these new cells mature and become neurons, as determined by triple labeling for BrdU and neuronal- or glial-specific markers. These findings raise the possibility that increased cell proliferation and increased neuronal number may be a mechanism by which antidepressant treatment overcomes the stress-induced atrophy and loss of hippocampal neurons and may contribute to the therapeutic actions of antidepressant treatment.

Animals↗

PubMed2002

Assessing antidepressant activity in rodents: recent developments and future needs.

Animal models are indispensable tools in the search to identify new antidepressant drugs and to provide insights into the neuropathology that underlies the idiopathic disease state of depression. As new targets are developed, both serendipitously and through hypothesis-driven research, existing animal paradigms are being modified and new tests are being developed to detect antidepressant actions of compounds acting on a broad range of neural and genetic targets. This review focuses on recent findings regarding some of the most widely employed animal models used currently to predict antidepressant potential. Emphasis is placed on recent modifications to such paradigms that have increased their utility and reliability. Furthermore, some key issues that need to be addressed for future discovery of novel antidepressant agents are examined, and the available data on genetically altered mice that might lead to the discovery of novel targets for antidepressant action are collated.

Animals↗

PubMed1999

Are antidepressants all the same? Surveying the opinions of Australian psychiatrists.

OBJECTIVE: Controlled trials do not suggest differences in efficacy between antidepressant compounds. Psychiatrists, however, frequently express the view that real differences do exist and are relevant to clinical practice. Since multiple comparative trials are not feasible, an alternative method for expanding the evidence base is to survey regularly the opinions of practising psychiatrists. METHOD: Two surveys of psychiatrists' opinions were conducted. Participants in the first survey were drawn from contact with 'SPHERE: A National Depression Project', while those in the second survey responded to a brief questionnaire distributed with Australasian Psychiatry. RESULTS: Reported volumes of scripts written, ratings of efficacy and tolerability, and preferences in specific clinical situations indicate that clinical psychiatrists now strongly prefer the newer antidepressant agents. They rate serotonin and noradrenalin re-uptake inhibitors (SNRIs) and selective serotonin re-uptake inhibitors (SSRIs) highest for antidepressant efficacy, serotonin receptor subtype 2 (5HT2) antagonists and some SSRIs highest for anti-anxiety efficacy, and some SSRIs and reversible inhibitors of monoamine oxidase inhibitor-A (RIMAs) lowest for side-effect burden. Further, SSRIs were their first preferences for most clinical situations. Serotonin and noradrenalin re-uptake inhibitors were the preferred choice for treatment-resistant depression and patients who had failed to respond to one SSRI. Serotonin receptor subtype 2 antagonists were the second choice to SSRIs for mixed anxiety and depression, and major depression with sleep disturbance. Reversible inhibitors of monoamine oxidase inhibitor-A were the second choice to SSRIs for adolescents with major depression, patients aged over 65 years, patients with serious medical illnesses and patients with chronic fatigue. Tricyclic antidepressants (TCAs) were the preferred choice for patients with chronic pain, and second choice to SSRIs for patients with major depression with panic disorder, postnatal disorders and patients with psychotic depression. CONCLUSION: Psychiatrists believe that important differences do exist between available antidepressant compounds. Such opinions are divergent from limited controlled data but may be influenced by a wide range of factors other than direct clinical experience. The role of such surveys in ongoing evaluation of clinical practice is emphasised.

Adult↗

PubMed2001

Repeated electroconvulsive stimulation, but not antidepressant drugs, induces mossy fibre sprouting in the rat hippocampus.

Electroconvulsive stimulation (ECS) has been shown recently to induce axonal sprouting of granule cells in the rodent hippocampus. This may relate to the clinical efficacy of electroconvulsive therapy (ECT) in humans. We compared the effects of three different clinically effective antidepressant treatments on mossy fibre sprouting in the rat dentate gyrus using Timm's histochemistry: (1) repeated spaced ECS; (2) daily administration for 4 weeks of the serotonin re-uptake inhibitor fluoxetine (1 mg/kg); and (3) daily administration for 4 weeks of the noradrenaline re-uptake inhibitor desipramine (5 mg/kg). The effect of subconvulsive electrical stimulation was also examined. Repeated ECS-induced sprouting while subconvulsive stimulation (which is ineffective clinically) did not. The two well-established chemical antidepressant therapies were also ineffective, indicating that induction of mossy fibre sprouting is not a common property of effective antidepressant agents. It is possible that the ability to induce sprouting might relate to the superior efficacy of ECT when compared to chemical antidepressants in clinical practice. Alternatively, it may contribute to the transient cognitive impairment that accompanies ECS in humans and other species.

Adrenergic Uptake Inhibitors↗

PubMed1997

Electroconvulsive therapy vs. paroxetine in treatment-resistant depression -- a randomized study.

Failure to respond to adequate pharmacological treatment for major depression is now the most common indication for the use of electroconvulsive therapy (ECT). The advantages of ECT with respect to both speed and quality of response are clinically important issues, but surprisingly few studies have examined the efficacy of ECT in relation to newer antidepressant agents such as selective serotonin reuptake inhibitors (SSRIs). A total of 39 subjects with major depression and with at least two failed antidepressant trials (mean 4.9 trials) were randomized to either paroxetine treatment (n=18) or right unilateral (RUL) ECT (n=21). Up to the end of the study treatment we found a reduction in the HAMD score of 59% for the ECT group and of 29% for the paroxetine group (P<0.001 paired t-test). In the ECT group, 71% of subjects fulfilled the response criteria (at least a 50% decrease in total HAMD score). The present study found ECT to be superior to paroxetine in medication-resistant major depression, in terms of both degree and speed of response.

Adult↗

PubMed1995

Venlafaxine. A review of its pharmacology and therapeutic potential in depression.

Venlafaxine is a phenylethylamine derivative which facilitates neurotransmission in the brain by blocking presynaptic reuptake of serotonin (5-hydroxytryptamine: 5-HT) and noradrenaline (norepinephrine). Clinical data from patients with major depression are consistent with the favourable efficacy and tolerability profile of venlafaxine predicted by pharmacodynamic studies. In patients with major depression, venlafaxine 75 to 375 mg/day administered for 6 weeks was significantly more effective than placebo, and at least as effective as imipramine, clomipramine, trazodone or fluoxetine. Venlafaxine is well tolerated, being associated with fewer anticholinergic and CNS adverse effects than tricyclic antidepressants. Unlike the tricyclic antidepressants, venlafaxine does not appear to significantly affect cardiac conduction, although there have been a few reports of modest increases in blood pressure, particularly after high doses of the drug. In conclusion, wider clinical experience is required to better characterise and confirm potential advantages of venlafaxine compared with other antidepressant agents. These advantages may include a rapid onset of action and reduced propensity to cause anticholinergic effects and cardiotoxicity compared with tricyclic antidepressants. Nevertheless, at this stage venlafaxine offers a more attractive treatment option than tricyclic antidepressants for patients with major depression, primarily because of its good overall tolerability profile.

Animals↗

PubMed2001

Evidence of early onset of antidepressant effect in randomized controlled trials.

Although antidepressant medications are effective in approximately 70% of patients with major depressive disorder, they have a delayed onset of therapeutic effect. This latency is problematic in that it prolongs the impairments associated with depression, leaves patients vulnerable to an increased risk of suicide, increases the likelihood that a patient will prematurely discontinue therapy, and increases medical costs associated with severe depression. No adequately designed prospective trials have been conducted to evaluate comparative time to onset of antidepressant effect. However, evidence suggests that some antidepressant agents may begin to work faster than others. Citalopram, venlafaxine, and mirtazapine each have exhibited statistically significant differences in some measures of antidepressant action within the first 2 weeks of treatment, both in placebo-controlled trials and in head-to-head comparisons with other antidepressants. This article reviews the data that hint at these drug-specific differences in time to onset of action. Given the potential benefits of early-acting antidepressant treatments, the possibility of superior speed of onset of citalopram, venlafaxine, and mirtazapine presented here merits further study in adequately designed, prospective clinical trials.

Antidepressive Agents↗

PubMed2002

Pharmacotherapy to sustain the fully remitted state.

Full remission should be the goal of antidepressant therapy; anything less leaves the patient with residual symptoms and an increased risk of relapse and recurrence. Most antidepressant agents offer similar rates of response, but there are some differences in the ability of different agents to promote a full remission. The greatest chance of achieving full remission occurs early in the course of treatment; thus, initial antidepressant strategies should be those that have the greatest therapeutic potential. Other strategies that may help improve the chances of achieving full remission include optimizing drug dosages and using combination and augmentation strategies. Failure to achieve full remission and early discontinuation of antidepressant therapy have been associated with a greater incidence of relapse and recurrence. Continued antidepressant therapy has clearly been shown to effectively reduce the probability of relapse and recurrence by about half compared with placebo. Therefore, once a patient achieves remission, it is important to continue the same antidepressant therapy for at least 6-12 months and, for many patients, considerably longer. Medication should continue at the dose that was initially effective because using low-dose maintenance therapy appears to decrease the protective benefits.

Antidepressive Agents↗

PubMed1996

The management of treatment resistance in depressed patients with substance use disorders.

General principles for treatment-resistant psychiatric disorders include reevaluation of diagnosis, search for hidden comorbidity, and systematic trials of alternative treatments and treatment combinations. For the combination of refractory depression and substance abuse, alternative approaches to both problems need to be tried, as suggested in the decision tree in Figure 1. Recognition of a previously unappreciated substance abuse problem or institution of more effective substance abuse treatment (see Table 2) can improve the outcome of depression. Hospitalization is often useful to enforce abstinence and to clarify the diagnosis of depression, and is particularly indicated if substance abuse is severe. If hospitalization is not possible then features of the history, such as relative onsets of depression and substance abuse, can be considered to support the diagnosis. TCAs and SSRIs have been studied in depressed substance abusers and should be the first lines of treatment. If these fail, other medications, medication combinations, or ECT should be considered, extrapolating from the general literature on treatment of refractory depression. In general, single agents should be preferred to combinations, as this reduces the odds of drug-drug interactions in patients who may abuse a variety of substances. Impairment by antidepressant agents of hepatic metabolism of other drugs should be considered, and sertraline, for example, might be preferred over fluoxetine for this reason. For each case, the known side effects and risks of a given antidepressant medication must be considered in the context of a patient's substance abuse pattern and medical problems. Such risk:benefit analyses are often difficult, as illustrated in the cases presented. Finally, although it is a rare occurrence, antidepressant medications that are anticholinergic or amphetamine-like may be abused, and this needs to be monitored. Alcohol or drug abuse history is a likely risk factor for benzodiazepine abuse, and benzodiazepines should, therefore, be avoided or used with caution. These recommendations for management of treatment-resistant depression with substance abuse are based upon clinical experience and extrapolation from the literature on treatment-resistant depression, treatment of substance abuse, and initial treatment of depression in substance abusers with TCAs and SSRIs. More treatment research is needed, particularly on Type IV patients where both depression and substance use are treatment resistant.

Adult↗

PubMed2006

Suicidality in pediatric patients treated with antidepressant drugs.

CONTEXT: There has been concern that widely used antidepressant agents might be associated with an increased risk of suicidal ideation and behavior (suicidality) in pediatric patients. OBJECTIVE: To investigate the relationship between antidepressant drugs and suicidality in pediatric patients participating in randomized, placebo-controlled trials. DATA SOURCES: Data were derived from 23 trials conducted in 9 drug company-supported programs evaluating the effectiveness of antidepressants in pediatric patients and 1 multicenter trial (the Treatment for Adolescents With Depression Study) that evaluated fluoxetine hydrochloride. STUDY SELECTION: All placebo-controlled trials submitted to the Food and Drug Administration were eligible for inclusion. Evaluable data were derived from 4582 patients in 24 trials. Sixteen trials studied patients with major depressive disorder, and the remaining 8 studied obsessive-compulsive disorder (n = 4), generalized anxiety disorder (n = 2), attention-deficit/hyperactivity disorder (n = 1), and social anxiety disorder (n = 1). Only 20 trials were included in the risk ratio analysis of suicidality because 4 trials had no events in the drug or placebo groups. DATA EXTRACTION: Individual patient data were available for all the trials. DATA SYNTHESIS: A meta-analysis was conducted to obtain overall suicidality risk estimates for each drug individually, for selective serotonin reuptake inhibitors in depression trials as a group, and for all evaluable trials combined. There were no completed suicides in any of these trials. The multicenter trial was the only individual trial to show a statistically significant risk ratio (4.62; 95% confidence interval [CI], 1.02-20.92). The overall risk ratio for selective serotonin reuptake inhibitors in depression trials was 1.66 (95% CI, 1.02-2.68) and for all drugs across all indications was 1.95 (95% CI, 1.28-2.98). The overall risk difference for all drugs across all indications was 0.02 (95% CI, 0.01-0.03). CONCLUSION: Use of antidepressant drugs in pediatric patients is associated with a modestly increased risk of suicidality.

Adolescent↗

PubMed2005

Differential behavioral effects of the antidepressants reboxetine, fluoxetine, and moclobemide in a modified forced swim test following chronic treatment.

RATIONALE: The forced swim test (FST) is the most widely used model for assessing potential antidepressant activity in rodents following acute or short-term treatment. However, few studies have compared the effects of short- and long-term antidepressant treatment on behaviors in the test, despite the need to treat patients chronically to produce clinical effects. OBJECTIVES: The current studies examined whether antidepressants from different classes produce different behavioral effects following short-term treatment and whether such effects change following administration for a longer duration. METHODS: The effects of administering short-term (3 days) and long-term (14 days) treatments of antidepressants from three different chemical classes with distinct mechanisms of action via osmotic minipump were examined: the selective norepinephrine reuptake inhibitor reboxetine (10 and 60 mg kg(-1) day(-1)), the selective serotonin reuptake inhibitor fluoxetine (2.5 and 15 mg kg(-1) day(-1)), and the reversible inhibitor of monoamine oxidase moclobemide (2.5 and 15 mg kg(-1) day(-1)). All testing was carried out in a 15-min test with no preswim session in order to negate any confounding aspect of an induction procedure. RESULTS: The majority of antidepressant-sensitive behavioral changes were observed in the first 5 min of the test. The low dose of reboxetine failed to alter behavior in the test after 3 days but significantly decreased immobility and increased climbing behavior following administration for 14 days, whereas the high dose of reboxetine was equally effective following 3 and 14 days of treatment. In a similar fashion, the low dose of fluoxetine failed to alter behavior in the test following 3 days, but showed an augmented response on immobility and increased swimming following administration for 14 days. The high dose of fluoxetine was slightly more effective at reducing immobility following administration for 14 days than 3 days. The low dose of moclobemide decreased immobility and increased climbing behavior following treatment for 3 days, but increases in both swimming and climbing behaviors were measured following treatment for 14 days. Treatment with the high dose of moclobemide for 3 days decreased immobility and increased swimming, whereas treatment for 14 days significantly increased both active behaviors (swimming and climbing). CONCLUSIONS: Antidepressants from three different classes produce different effects on active behaviors in the FST. The effects of antidepressants were augmented following chronic administration for 14 days, especially when given at low doses. This suggests that modifications of the FST can be used to examine the onset of action of antidepressant agents produced by long-term administration.

Animals↗

PubMed1988

8-Hydroxy-2-(di-n-propylamino)tetralin, a selective serotonin1A receptor agonist, reduces the immobility of rats in the forced swimming test by acting on the nucleus raphe dorsalis.

8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a selective serotonin1A (5-HT1A) receptor agonist, was studied for its anti-immobility activity in the forced swimming test when administered into the raphe nuclei medianus and dorsalis of rats. At concentrations ranging from 0.5 to 5 micrograms, 8-OH-DPAT significantly reduced the immobility of rats when administered into the nucleus raphe dorsalis, but only 5 micrograms was effective when administered into the nucleus medianus. The activity of rats in an open-field under conditions identical to those used in the forced swimming test was not significantly changed by various concentrations of 8-OH-DPAT administered into the nucleus raphe dorsalis, but was significantly increased by an infusion of 5 micrograms 8-OH-DPAT into the nucleus raphe medianus. The effect of an infusion of 1 micrograms 8-OH-DPAT into the nucleus dorsalis was prevented by infusing 2.5 micrograms (-)-propranolol or 2.5 micrograms (-)-pindolol into the same area 5 min before 8-OH-DPAT or by treating the animals with sulpiride systemically (100 mg/kg i.p.) or centrally (in the nucleus accumbens; 1 microgram/0.5 microliter). The results suggest that 8-OH-DPAT reduces the immobility of rats by activating dopamine transmission, probably in the nucleus accumbens, as a consequence of its ability to reduce the activity of 5-HT neurons that originate in the nucleus raphe dorsalis. In view of the similarities between the effects of well-established antidepressants and 8-OH-DPAT in the forced swimming test, it is suggested that 5-HT1A receptor agonists may constitute a novel class of antidepressant agents.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed2002

Reduction of cGMP and nitric oxide has antidepressant-like effects in the forced swimming test in rats.

The forced swimming test (FST) has been extensively used as a screening model for new antidepressant agents. It has been shown that drugs which reduce the amount of nitric oxide (NO) have the same outcome in this model as classic antidepressants. In addition, previous studies have shown that methylene blue, which acts as a direct inhibitor of both NOS and soluble guanylate cyclase (sGC), mimics the effect of clinically effective antidepressants in patients and in the FST. The present study examined the effects of the specific inhibitor of the NO-sGC pathway, [1H-[1,2,4]Oxadiazole[4,3-a]quinoxalin-1-one] (ODQ) and of the neuronal NOS inhibitor 7-nitroindazole (7-NI) in the FST. We found that ODQ (10 and 20 mg/kg) significantly decreased the immobility time in the FST compared to the control. Similarly, injections of 7-NI (30 or 60 mg/kg) reduced immobility time as well as Imipramine (IMI, 30 mg/kg). Interestingly, L-Arginine (250 mg/kg) administered in combination with ODQ reversed the effect of ODQ but displayed no effect when administered alone. Locomotion activity was significantly decreased following administration of IMI (30 mg/kg) and 7-NI (30 and 60 mg/kg) but was unaffected after administration of ODQ (10 and 20 mg/kg). These findings suggest that the NO-sGC-cGMP pathway may play an important role in the mediation of the behavioural effect in the FST without influence on motor activity.

Animals↗